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Background: Gastric cancer (GC) is a common tumor found worldwide, and cisplatin is the first-line agent for the treatment of GC. However, the resistance to cisplatin is an obstacle. Here, we aim to explore the biological mechanism of long noncoding RNA regulator of reprogramming (ROR) in the cisplatin resistance of GC. Materials and Methods: ROR, miR-519d-3p, and high mobility group protein A2 (HMGA2) expression in GC tissues and cells were measured by quantitative real-time polymerase chain reaction and Western blot. Cell viability, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry, respectively. The relative protein expression was detected by Western blot. The interactions between miR-519d-3p and ROR, HMGA2 were predicted using miRcode and starBase v2.0 online database, and then verified by dual luciferase reporter assay and RNA immunoprecipitation assay. In addition, the xenograft tumor mouse model was constructed to verify the biological role of ROR in vivo. Results: The levels of ROR, HMGA2 were significantly upregulated, and miR-519d-3p was apparently downregulated in GC tissues and cells. The miRcode and starBase v2.0 online websites and dual luciferase reporter assay validated that miR-519d-3p directly interacted with ROR and HMGA2. Furthermore, ROR knockdown downregulated HMGA2 to restrain cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cisplatin resistance in GC cells by targeting miR-519d-3p. In addition, the depletion of ROR repressed the xenograft tumor growth in vivo. Conclusion: In conclusion, we first found the ROR/miR-519d-3p/HMGA2 regulatory network to regulate cell proliferation, migration, invasion, EMT, and cisplatin resistance in GC, and this may shed light on the GC tumorigenesis.

Long non-coding RNAs (lncRNAs) are a novel class of non-coding RNA (ncRNA), that have been studied extensively in the field of tumor research in recent years. In the case of tumor-associated lncRNAs, lncRNA cytoskeleton regulator RNA (CYTOR) displays extensive functions in tumorigenesis, including invasion, metastasis, malignant proliferation, glycolysis, and inflammatory response. Moreover, the dysregulation of CYTOR is closely related to clinicopathological characteristics, such as tumor stage, lymph node metastasis and infiltration, and poor prognosis of tumor patients. In this review, we provide a novel strategy to summarize the biological functions and clinical value of CYTOR in tumors through an overview of the literature combined with gene set enrichment analysis. A deeper understanding of the role of CYTOR in tumorigenesis may provide new diagnostic, prognostic and therapeutic markers for human tumors.

Objective Heat exposure and heat stress/strain is a concern for many workers. There is increasing interest in potential chronic health effects of occupational heat exposure, including cancer risk. We examined potential associations of occupational heat exposure and colorectal cancer (CRC) risk in a large Spanish multi-case–­control study. Methods We analyzed data on 1198 histologically confirmed CRC cases and 2690 frequency-matched controls. The Spanish job-exposure matrix, MatEmEsp, was used to assign heat exposure estimates to the lifetime occupations of participants. Three exposure indices were assessed: ever versus never exposed, cumulative exposure and duration (years). We estimated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression adjusting for potential confounders. Results Overall, there was no association of ever, compared with never, occupational heat exposure and CRC (OR 1.09, 95% CI 0.92–1.29). There were also no associations observed according to categories of cumulative exposure or duration, and there was no evidence for a trend. There was no clear association of ever occupational heat exposure and CRC in analysis conducted among either men or women when analyzed separately. Positive associations were observed among women in the highest categories of cumulative exposure (OR 1.81, 95% CI 1.09–3.03) and duration (OR 2.89, 95% CI 1.50–5.59) as well as some evidence for a trend (P, Instituto de Salud Carlos III, Instituto de Salud Carlos III European Union (EU) Spanish Government PI08/1770 PI08/1359 PI09/00773 PI09/01286 PI09/01903 PI09/02078 PI09/01662 PI11/01403 PI11/01889 PI12/00265, Junta de Andalucia 2010ACUP 00310, Conselleria de Sanitat of the Generalitat Valenciana FOOD-CT-2006-036224-HIWATE, La Caixa Foundation 2014SGR647, Regional government of the Basque Country, European Union (EU) European Commission Joint Research Centre 2017SGR1085, Spanish Association Against Cancer (AECC) Scientific Foundation, Catalan Government DURSI RYC-2017-01892, Instituto de Salud Carlos III CEX2018-000806-S, Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia, Junta de Castilla y Leon, Principality of Asturias, Consejeria de Sanidad de la Region de Murcia, Spanish Government, University of Oviedo, Spanish Ministry of Science, Innovation and Universities - European Social Fund, Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa LE22A10-2, Generalitat de Catalunya through the CERCA Program 2009-S0143 AP_061/10

Human papillomavirus (HPV) infection is a causative agent of multiple human cancers, including cervical and head and neck cancers. In these HPV-positive tumors, somatic mutations are caused by aberrant activation of DNA mutators such as members of the apolipoprotein B messenger RNA–editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytidine deaminases. APOBEC3 proteins are most notable for their restriction of various viruses, including anti-HPV activity. However, the potential role of APOBEC3 proteins in HPV-induced cancer progression has recently garnered significant attention. Ongoing research stems from the observations that elevated APOBEC3 expression is driven by HPV oncogene expression and that APOBEC3 activity is likely a significant contributor to somatic mutagenesis in HPV-positive cancers. This review focuses on recent advances in the study of APOBEC3 proteins and their roles in HPV infection and HPV-driven oncogenesis. Further, we discuss critical gaps and unanswered questions in our understanding of APOBEC3 in virus-associated cancers.

In this review, we summarize the biological roles of methionine, methionine adenosyl transferase 2A (MAT2A) and S -adenosyl methionine (SAM) in methylation reactions during tumorigenesis. Newly emerged inhibitors targeting the methionine-MAT2A-SAM axis will be discussed.SAM is the critical and global methyl-donor for methylation reactions regulating gene expression, and in mammalian cells, it is synthesized by MAT2A using methionine. Recent studies have validated methionine and MAT2A as metabolic dependencies of cancer cells because of their essential roles in SAM biosynthesis. MAT2A inhibition leads to synthetic lethality in methylthioadenosine-phosphorylase (MTAP)-deleted cancers, which accounts for 15% of all cancer types. Of note, remarkable progress has been made in developing inhibitors targeting the methionine-MAT2A-SAM axis, as the first-in-class MAT2A inhibitors AG-270 and IDE397 enter clinical trials to treat cancer.The methionine-MAT2A-SAM axis plays an important role in tumorigenesis by providing SAM as a critical substrate for abnormal protein as well as DNA and RNA methylation in cancer cells. Targeting SAM biosynthesis through MAT2A inhibition has emerged as a novel and promising strategy for cancer therapy.

Accumulating evidence has unfolded the significance of extracellular vesicles (EVs) in diseases and cancers. Here, we attempted to discuss the role of cancer-associated fibroblasts (CAFs)-derived EVs containing miR-199a-5p in gastric tumorigenesis. Upregulated miR-199a-5p was first identified in cancer cells. Then, we selected CAFs for isolation of EVs which were co-cultured with AGS cells. We observed successful delivery of miR-199a-5p via CAF-derived EVs. Besides, miR-199a-5p promoted malignant properties of AGS cells. Moreover, miR-199a-5p downregulated FKBP5, leading to upregulated phosphorylation level of AKT1, which promoted the malignant phenotypes of AGS cells by activating mammalian target of rapamycin complex 1(mTORC1). Exosomal miR-199a-5p from CAFs promoted gastric tumorigenesis

The cGAS/STING signaling pathway is an important part of the cytoplasmic DNA sensor, which can trigger a type I interferon response to microbial infection when pathogenic DNA is detected. However, continuous inhibition of cGAS/STING signaling by viral infection may be an important cause of tumorigenesis. At the same time, recent studies have shown that although the cGAS/STING signaling pathway also plays a core role in anti-tumor immunity and cell senescence, the inflammatory response induced by cGAS/STING signaling will also promote tumorigenesis in different backgrounds. Here, we discuss the role of cGAS/STING in the context of infection, senescence, and tumors, especially with respect to progression, to facilitate a better understanding of the mechanism of the cGAS/STING pathway.

Melanoma is one of the most dangerous types of cutaneous neoplasms, which are pigment-producing cells of neuroectodermal origin found all over the body. A great deal of research is focused on the mechanisms of melanoma to promote better diagnostic and treatment options for melanoma in its advanced stages. The progression of melanoma involves alteration in different levels of gene expression. With the successful implementation of next-generation sequencing technology, an increasing number of long noncoding RNAs (lncRNAs) sequences have been discovered, and a significant number of them have phenotypic effects in both in vitro and in vivo studies, implying that they play an important role in the occurrence and progression of human cancers, particularly melanoma. A number of evidence indicated that lncRNAs are important regulators in tumor cell proliferation, invasion, apoptosis, immune escape, energy metabolism, drug resistance, epigenetic regulation. To better understand the role of lncRNAs in melanoma tumorigenesis, we categorize melanoma-associated lncRNAs according to their cellular functions and associations with gene expression and signaling pathways in this review. Based on the mechanisms of lncRNA, we discuss the possibility of lncRNA-target treatments, and the application of liquid biopsies to detect lncRNAs in melanoma diagnosis and prognosis.

Signal transducer and activator of transcription 3 (STAT3) is known as a pro-oncogenic transcription factor. Regarding liver carcinogenesis, however, it remains controversial whether activated STAT3 is pro- or anti-tumorigenic. This study aimed to clarify the significance and mechanism of STAT3 activation in hepatocellular carcinoma (HCC).Hepatocyte-specific Kras-mutant mice (Alb-Cre KrasTumors in KrasSTAT3 is activated by CTGF-mediated tumor-stroma crosstalk to promote HCC progression. STAT3-CTGF positive feedback loop could be a therapeutic target.

Air pollution is a global health threat and causes millions of human deaths annually. Outdoor and indoor air pollutants such as polycyclic aromatic hydrocarbons (PAHs) are the most prevalent cause of respiratory disorders, lung disease, pregnancy disorders, endocrine disturbances, diabetes, obesity, cardiovascular disease and cancer because pollutants can alter gene expression via epigenetics like DNA methylation and histone modifications which can initiate tumorigenesis and progressed to cancer. Carcinogenicity of PAHs can be eliminated by endogenous melatonin hormone (MT) via binding to its receptor (MTNR1A) that act as free radicals scavenger therefore it protects the body from developing occupational cancer. Aims of study To predict the protective effect of melatonin hormone as anti-cancer through binding to its receptor (MTNR1A) against any type of cancer that can be induced by chronic exposure to air pollutants. Subjects and methods This study includes 168 participants, they have been divided into three groups (control, refinery field workers and refinery office workers). PAH was analyzed for each participant by GC/MS whereas melatonin hormone and MTNR1A were measured by ELISA technique. Results PAHs were absent in the blood of control, and they were elevated in refinery worker’s specimens. Concentration of MT was higher in field worker than in office and control group as well as MTNR1A, also there is a relation between their levels and duration of exposure. Conclusion Exposure to PAHs can lead to oxidative stress that can damage DNA resulting in many types of cancer but this carcinogenic effects of PAHs can be eliminated by natural endogenous biomolecules such as MT and its receptor (MTNR1A) therefore their elevation has a beneficial effect as anti-cancer to reduce the oxidative stress and prevent tumorigenesis.

Cellular senescence forms a barrier to tumorigenesis, by inducing cell cycle arrest in damaged and mutated cells. However, once formed, senescent cells often emit paracrine signals that can either promote or suppress tumorigenesis. There is evidence that, in addition to cancer cells, subsets of tumor stromal cells, including fibroblasts, endothelial cells, and immune cells, undergo senescence. Such senescent stromal cells can influence cancer development and progression and represent potential targets for therapy. However, understanding of their characteristics and roles is limited and few studies have dissected their functions in vivo. Here, we discuss current knowledge and pertinent questions regarding the presence of senescent stromal cells in cancers, the triggers that elicit their formation, and their potential roles within the tumor microenvironment.

Chronic inflammation caused by persistent infections and metabolic disorders is thought to contribute to the increased cancer risk and the accelerated cancer progression. Oppositely, acute inflammation induced by bacteria-based vaccines or that is occurring after cancer selectively inhibits cancer progression and metastasis. However, the interaction between inflammation and cancer may be more complex than the current explanations for the relationship between chronic and acute inflammation and cancer. In this review, we described the impact of inflammation on cancer on the basis of three perspectives, including inflammation with different durations (chronic and acute inflammation), different scopes (systemic and local inflammation) and different occurrence sequences (inflammation occurring after and before cancer). In addition, we also introduced bacteria/virus-based cancer immunotherapies. We perceive that inflammation may be a double-edged sword with cancer-promoting and cancer-suppressing functions in certain cases. We expect to further improve the understanding of the relationship between inflammation and cancer and provide a theoretical basis for further research on their complex interaction.

Small cell lung cancer (SCLC) is a recalcitrant, relatively immune-cold, and deadly subtype of lung cancer. SCLC has been viewed as a single or homogenous disease that includes deletion or inactivation of the two major tumor suppressor genes (TP53 and RB1) as a key hallmark. However, recent sightings suggest the complexity of SCLC tumors that comprises highly dynamic multiple subtypes contributing to high intratumor heterogeneity. Furthermore, the absence of targeted therapies, the understudied tumor immune microenvironment (TIME), and subtype plasticity are also responsible for therapy resistance. Secretory chemokines play a crucial role in immunomodulation by trafficking immune cells to the tumors. Chemokines and cytokines modulate the anti-tumor immune response and wield a pro-/anti-tumorigenic effect on SCLC cells after binding to cognate receptors. In this review, we summarize and highlight recent findings that establish the role of chemokines in SCLC growth and metastasis, and sophisticated intratumor heterogeneity. We also discuss the chemokine networks that are putative targets or modulators for augmenting the anti-tumor immune responses in targeted or chemo-/immuno-therapeutic strategies, and how these combinations may be utilized to conquer SCLC.

Osteosarcoma (OS) is the most common primary malignant bone tumor and is mainly diagnosed in children. Toll-like receptor 9 (TLR9) is expressed in various tumor cells and was correlated with cancer progression. However, the underlying mechanism of TLR9 on the OS progression remains unclear. Our previous study demonstrated that the expression of TLR9 was positively correlated with the development stage of OS. Herein, we further evaluated the actual roles and the molecular mechanism of TLR9 on regulating OS cell proliferation and metastasis. Our data showed that TLR9 was upregulated in OS cells compared to normal osteoblastic cells, and knockdown of TLR9 inhibited OS cell proliferation and induced cell cycle arrest by the decreased expression of cyclin D1, CDK2, and p-Rb, while TLR9 overexpression exerted the inverse effects. Furthermore, TLR9 overexpression could enhance the migration and invasion activities of the OS cells by the upregulation of matrix metalloproteinases 2 (MMP2) and MMP9, and the opposite result was observed in TLR9-silenced cells. Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.

PUF60 (Poly (U) binding splicing factor 60 kDa), a nucleic acid-binding protein, has been shown to regulate transcription and links to tumorigenesis in various cancers. However, its biological role and function in glioblastoma remain unknown. In this study, we found that PUF60 is highly expressed in glioblastoma and correlated with poor prognosis. Furthermore, PUF60 knockdown significantly decreased the proliferation of glioblastoma cells in vitro and in vivo. Mechanistically, PUF60 could reduce the ubiquitination level of EGFR by transcriptionally regulating STUB1, an E3 ubiquitin ligase of EGFR, which lead to the activation of the EGFR-AKT pathway. Collectively, our study reveals the oncogenic role of PUF60 in glioblastoma and provides a potential therapeutic target for glioblastoma treatment.

The mechanisms governing the development and progression of cancers are believed to be the consequence of hereditary deformities and epigenetic modifications. Accordingly, epigenetics has become an incredible and progressively explored field of research to discover better prevention and therapy for neoplasia, especially triple-negative breast cancer (TNBC). It represents 15–20% of all invasive breast cancers and will, in general, have bellicose histological highlights and poor clinical outcomes. In the early phases of triple-negative breast carcinogenesis, epigenetic deregulation modifies chromatin structure and influences the plasticity of cells. It up-keeps the oncogenic reprogramming of malignant progenitor cells with the acquisition of unrestrained selfrenewal capacities. Genomic impulsiveness in TNBC prompts mutations, copy number variations, as well as genetic rearrangements, while epigenetic remodeling includes an amendment by DNA methylation, histone modification, and noncoding RNAs of gene expression profiles. It is currently evident that epigenetic mechanisms assume a significant part in the pathogenesis, maintenance, and therapeutic resistance of TNBC. Although TNBC is a heterogeneous malaise that is perplexing to describe and treat, the ongoing explosion of genetic and epigenetic research will help to expand these endeavors. Latest developments in transcriptome analysis have reformed our understanding of human diseases, including TNBC at the molecular medicine level. It is appealing to envision transcriptomic biomarkers to comprehend tumor behavior more readily regarding its cellular microenvironment. Understanding these essential biomarkers and molecular changes will propel our capability to treat TNBC adequately. This review will depict the different aspects of epigenetics and the landscape of transcriptomics in triple-negative breast carcinogenesis and their impending application for diagnosis, prognosis, and treatment decision with the view of molecular medicine.

The Class I

Phosphoglycerate kinase 1 (PGK1) catalyzes the conversion of 1,3-bisphosphoglyceride (1,3-BPG) and ADP into 3-phosphate (3-PG) and ATP, which is a key process of glycolysis. PGK1 is considered a major regulator of various events, including one-carbon metabolism, serine biosynthesis and cell redox regulation. In the past decade, PGK1 has been found to be closely associated with various malignancies, making it a potential therapeutic target. PGK1 is involved in a series of biological processes related to tumorigenesis through post-translational modifications and various signaling pathways. PGK1 not only can participate in glucose metabolism but also acts as a protein kinase to participate in EMT, autophagy, angiogenesis, DNA replication and other processes related to tumor development. However, PGK1 also acts as a disulfide reductase to inhibit tumor by affecting angiogenesis. Exploring the structure, function and posttranslational modification of PGK1 will be helpful in further understanding the effect of metabolism on tumor progression. This manuscript reviews the role and mechanism of PGK1 in human malignancies, providing the theoretical basis for PGK1 as a possible clinical anticancer target.

KAT6A is considered a factor influencing carcinogenesis. Due to the fact that lung cancer is one of the leading causes of death, the aim of our study was to evaluate KAT6A expression in non-small cell lung cancer (NSCLC) tumors and the NSCLC cell line model.The expression of KAT6A was examined in NSCLC tumors by real-time PCR and immunohistochemistry. KAT6A expression was investigated in the NSCLC cell line model by real-time PCR, western blot, and immunofluorescence.KAT6A protein level was elevated in NSCLC tumors compared to non-malignant lung tissues (NMLT). The KAT6A mRNA expression in NSCLC, lung adenocarcinoma, and lung squamous cell carcinoma samples was differentiated. The results from the in vitro NSCLC model demonstrated elevated expression of KAT6A in lung cancer cell lines in comparison to normal lung fibroblasts.The outcomes showed an increased KAT6A protein level in NSCLC compared to control samples, which suggests the oncogenic role of KAT6A in this type of cancer. Therefore, targeting KAT6A in NSCLC might be worth consideration.

Indiscriminate usage and mismanagement of chemicals in the agricultural and industrial sectors have contaminated different environmental compartments. Exposure to these persistent and hazardous pollutants like heavy metals, endocrine disruptors, aromatic hydrocarbons, and pesticides can result in various health adversities, including cancer. Chemical carcinogens follow a similar pattern of carcinogenesis, like oxidative stress, chromosomal aberration, DNA double-strand break, mismatch repair, and misregulation of oncogenic and/or tumor suppressors. Out of several cancer-associated endpoints, cellular metabolic homeostasis is the commonest to be deregulated upon chemical exposure. Chemical carcinogens hamper glycolytic reprogramming to fuel the malignant transformation of the cells and/or promote cancer progression. Several regulators like Akt, ERK, Ras, c-Myc, HIF-1α, and p53 regulate glycolysis in chemical-induced carcinogenesis. However, the deregulation of the anabolic biochemistry of glucose during chemical-induced carcinogenesis remains to be uncovered. This review comprehensively covers the environmental chemical-induced glycolytic shift during carcinogenesis and its mechanism. The focus is also to fill the major gaps associated with understanding the fairy tale between environmental carcinogens and metabolic reprogramming. Although evidence from studies regarding glycolytic reprogramming in chemical carcinogenesis provides valuable insights into cancer therapy, exposure to a mixture of toxicants and their mechanism of inducing carcinogenesis still needs to be studied.

Occupational exposure to trichloroethylene (TCE) has been associated with alterations in B-cell activation factors and an increased risk of non-Hodgkin's lymphoma (NHL). Here, we aimed to examine the biological processes influenced by trichloroethylene (TCE) exposure to understand the underlying molecular mechanisms. This cross-sectional molecular epidemiology study included data of 1317 targeted proteins in the serum from 42 TCE exposed and 34 unexposed factory workers in Guangdong, China. We used multivariable linear regressions to identify proteins associated with TCE exposure and examined their exposure-response relationship across categories of TCE exposure (unexposed, low exposed:10 ppm, high exposed: ≥10 ppm). We further examined pathway enrichment of TCE-related proteins to understand their biological response. Occupational exposure to TCE was associated with lower levels of tumor necrosis factor receptor superfamily member 17 (TNFRSF17; β = -0.08; p-value=0.0003) and Kynureninase (KYNU; β = -0.10, p-value = 0.002). These proteins also showed a significant exposure-response relation across the unexposed, low exposed, and high exposed workers (all p-trends0.001, FDR0.20). Pathway analysis of TCE-related proteins showed significant enrichment (FDR0.05) for several inflammatory and immune pathways. TCE exposure was associated with TNFRSF17, a key B-cell maturation antigen that mediates B-cell survival and KYNU, an enzyme that plays a role in T-cell mediated immune response. Given that altered immunity is an established risk factor for NHL, our findings support the biological plausibility of linking TCE exposure with NHL. This article is protected by copyright. All rights reserved.

Colorectal cancer (CRC) is one of the main causes of malignancy-related mortality worldwide. It was well-identified that microRNAs (miRNAs) decisively participate in cellular biological pathways; in a way that their deregulated expression causes CRC progression. miRNAs can control the translation and degradation of mRNAs by binding to various molecular targets involved in different biological processes, including growth, apoptosis, cell cycle, autophagy, angiogenesis, metastasis, etc. The functions of these dysregulated miRNAs may be either oncogenic or tumor-suppressive. Therefore, these miRNAs can be contributed to prognostic, diagnostic, and therapeutic approaches in CRC. In this study, we reviewed the tumor-suppressive and oncogenic functions of miRNAs in CRC and assessed their molecular activities in CRC development. However, further investigation for the involvement of dysregulated miRNAs in CRC progression is required.

The initiation, progression, and relapse of cancers often result from mutations occurring within somatic cells. Consequently, processes that elevate mutation rates accelerate carcinogenesis and hinder the development of long-lasting therapeutics. Recent sequencing of human cancer genomes has identified patterns of mutations, termed mutation signatures, many of which correspond to specific environmentally induced and endogenous mutation processes. Some of the most frequently observed mutation signatures are caused by dysregulated activity of APOBECs, which deaminate cytidines in single-stranded DNA at specific sequence motifs causing C-to-T and C-to-G substitutions. In humans, APOBEC-generated genetic heterogeneity in tumor cells contributes to carcinogenesis, metastasis, and resistance to therapeutics. Here, we review the current understanding of APOBECs’ role in cancer mutagenesis and impact on disease and the biological processes that influence APOBEC mutagenic capacity.

The Regulator of Chromosome Condensation 2 (RCC2) is an important gene that regulates mitosis and cytoplasmic division in the cell cycle. Although there have been reported in several individual tumors, an integrative analysis of

Glycosphingolipids (GSLs) play numerous roles in cellular processes, including cell proliferation, apoptosis, inflammation, and cell signaling. Alteration of the GSLs metabolism leads to the accumulation of particular species of GSLs, which can lead to various pathologies, including carcinogenesis and metastasis; in essence, all neoplasms are characterized by the synthesis and aberrant organization of GSLs expressed on the cell surface. Secondary brain tumors make up the majority of intracranial cancers and generally present an unfavorable prognosis. In the present work, a native GSL mixture extracted and purified from a secondary brain tumor with primary pulmonary origin was obtained through extraction and purification and analyzed by MALDI TOF mass spectrometry. Research in the field of lipidomics could offer new data for the understanding of brain tropism and metastatic pathways, by studying the glycolipid molecules involved in the process of metastasis in general and in the production of brain metastases in particular. This could shed new light on the pattern of lipid glycosylation in secondary brain tumors, with a great impact on the effectiveness of cancer therapies, which could be adapted to the specific molecular pattern of the tumor.

FOXM1 acts as an oncogenic transcription factor and is involved in multiple hallmarks of human malignancies. Recent studies have demonstrated that FOXM1 is upregulated and correlated with poor prognosis in a majority of cancers. However, there are few pan-cancer analyses of FOXM1. This study aimed to investigate the expression profiles and clinical significance of FOXM1 in 31 types of solid tumors. We explored the expression profiles and the prognostic value of FOXM1 in pan-cancer across The Cancer Genome Atlas (TCGA). We further used lung adenocarcinoma (LUAD) tissues combined with quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) for experimental validation of FOXM1 expression. Besides, we verified the function of FOXM1 in a lung cancer cell line. Gene set enrichment analysis (GSEA) was conducted to explore signaling pathways related to FOXM1 expression. We observed that up-regulated FOXM1 was significantly related to poor survival in most tumors. Furthermore, there are significant correlations between FOXM1 expression and the infiltrating levels of different types of immune cells, TMB, MSI and immune checkpoint genes in a variety of cancers. Additional analysis based on IMvigor 210 cohort confirmed that patients with high level of FOXM1 exhibited a superior response to anti-PD-L1 therapy, and had a prolonged OS. In conclusion, this study indicated that FOXM1 could serve as a prognostic biomarker for most types of cancers and played a crucial role in the tumor immune microenvironment.

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.

Platinum-based chemotherapy drugs play a very important role in the treatment of patients with advanced colorectal cancer, but the drug resistance of platinum-based chemotherapy drugs is an important topic that puzzles us. If we can find mechanisms of resistance, it will be revolutionary for us. We analysed the differential genes, core genes and their enrichment pathways in platinum-resistant and non-resistant patients through a public database. Platinum-resistant cell lines were cultured in vitro for in vitro colony and Transwell analysis. Tumorigenesis analysis of nude mice in vivo. Verify the function of core genes. Through differential gene and enrichment analysis, we found that CUL4B was the main factor affecting platinum drug resistance and EMT. Our hypothesis was further verified by in vitro drug-resistant and wild-type cell lines and in vivo tumorigenesis analysis of nude mice. CUL4B leads to platinum drug resistance in colorectal cancer by affecting tumour EMT.

Epigallocatechin gallate and tetrahydrocurcumin are aminated as colonic metabolites, preserving their bioactivities and improving their capabilities. We compared the bioactivities of unaminated (CUR) and aminated (AC) curcumin in inflammatory colitis-associated tumorigenesis. The anti-inflammatory and anticancer capabilities of CUR and AC were evaluated using RAW264.7 and HT29 cell lines, respectively. An azoxymethane/dextran sodium sulfate-induced colitis-associated carcinogenesis mouse model was used with CUR and two-dose AC interventions. AC had a greater anti-inflammatory effect but a similar anticancer effect as CUR in vitro. CUR and low-dose AC (LAC) significantly preserved colon length and reduced tumor number in vivo. Both CUR and LAC inhibited activation of the protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling pathway, its downstream cytokines, and the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/c-myelocytomatosis oncogene (c-MYC) pathway. However, only LAC significantly preserved E-cadherin, reduced N-cadherin, and facilitated beneficial gut microbial growth, including

Extensive protein synthesis is necessary for uncontrolled cancer cell proliferation, requiring hyperactive ribosome biogenesis. Our previous Pan-cancer study has identified EXOSC8 as a potential copy number variation (CNV)-driven rRNA metabolism-related oncogene in colorectal cancer (CRC). Herein, we further investigated proliferation-prompting functions and mechanisms of EXOSC8 in CRC by performing in silico analyses and wet-lab experiments. We uncovered that increased EXOSC8 expression and CNV levels are strongly associated with ribosome biogenesis-related factor levels in CRC, including ribosome proteins (RPs), eukaryotic translation initiation factors and RNA polymerase I/III. EXOSC8 silence decreases nucleolar protein and proliferation marker levels, as well as rRNA/DNA and global protein syntheses. Clinically, EXOSC8 is upregulated across human cancers, particularly CNV-driven upregulation in CRC was markedly associated with poor clinical outcomes. Mechanistically, EXOSC8 knockdown increased p53 levels in CRC, and the oncogenic proliferation phenotypes of EXOSC8 depended on p53 in vitro and in vivo. We discovered that EXOSC8 knockdown in CRC cells triggers ribosomal stress, nucleolar RPL5/11 being released into the nucleoplasm and "hijacking" Mdm2 to block its E3 ubiquitin ligase function, thus releasing and activating p53. Furthermore, our therapeutic experiments provided initial evidence that EXOSC8 might serve as a potential therapeutic target in CRC. Our findings revealed, for the first time, that the RNA exosome gene (EXOSC8) promotes CRC tumorigenesis by regulating cancer-related ribosome biogenesis in CRC. This study further extends our previous Pan-cancer study of the rRNA metabolism-related genes. The inhibition of EXOSC8 is a novel therapeutic strategy for the RPs-Mdm2-p53 ribosome biogenesis surveillance pathway in CRC.

Emerging evidence shows that the lncRNA THOR is deeply involved in the development of various cancers. However, the effects and underlying molecular mechanisms of THOR in breast cancer (BRCA) initiation and progression have not been fully elucidated. Here we show that THOR is critical for BRCA tumorigenesis by interacting with hnRNPD to regulate downstream signaling pathways. THOR expression was significantly higher in BRCA tissues than in normal tissues, and THOR upregulation was associated with a poor prognosis in BRCA patients. Functionally, THOR knockdown impaired cell proliferation, migration and invasion in BRCA cells in vitro and inhibited tumorigenesis and metastasis in a tumor xenograft model and THOR-deficient MMTV-PyMT model in vivo. Mechanistically, THOR bound to the hnRNPD protein and increased hnRNPD protein levels by maintaining hnRNPD protein stability through inhibition of the proteasome-dependent degradation pathway. The increased hnRNPD protein levels led to stabilization of its target mRNAs, including pyruvate dehydrogenase kinase 1 (PDK1), further activating downstream PI3K-AKT and MAPK signaling pathways to regulate BRCA cell proliferation and metastasis. Together, our findings indicate that THOR is a promising prognostic predictor for BRCA patients and that the THOR-hnRNPD-PDK1-MAPK/PI3K-AKT axis might be a potential therapeutic target for BRCA treatment.

PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is an important signal transduction pathway mediated by enzyme-linked receptors with many biological functions in mammals. This pathway modulates the epigenetic modification of DNA and target gene histones and plays a significant role in regulating biological activity, disease progression, oncogenesis, and cancer progression. PI3K/AKT/mTOR signaling pathway involves and mediates many cellular processes such as nutrient uptake, proliferation, anabolic reactions, and cell survival. Several studies have shown that PI3K/AKT/mTOR has been a promising therapeutic approach to intracerebral hemorrhage (ICH). ICH is characterized by the progressive development of hematoma, which leads to the structural destabilization of the neurons and glial cells, leading to neuronal deformation, further contributing to mitochondrial dysfunction, membrane depolarization, oligaemia, and neurotransmitter imbalance. Partial suppression of cell metabolism and necrosis can occur, depending on the degree of mitochondrial dysfunction. Therefore in the following review, we discuss whether or not the activation of the PI3K/AKT/mTOR signaling pathway could minimize neuronal dysfunction following ICH. We further elaborate the review by discussing the updated pathophysiology of brain hemorrhage and the role of molecular targets in other neurodegenerative diseases. This review provides current approachable disease treatment in various disease states, single and dual PI3K/AKT/mTOR signaling pathway modulators.

Abstract: Colorectal cancer (CRC) is the third most prevalent malignant neoplasm in the world. CRC is influenced by both environmental and genetic factors. Through toxin-mediated DNA damage and the promotion of persistent dysregulated inflammation, the gut microbiota plays a crucial role in the development of CRC. In this review, we discussed the correlation between the bacterial microbiota and CRC carcinogenesis as well as the mechanism by which Streptococcus bovis/gallolyticus, Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli can cause CRC.

The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.

The persistent infection of high-risk Human papillomavirus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications.This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics.

Background: MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional regulation of genes. Deregulated expression of miRNAs is involved in different pathogenic mechanisms, particularly colorectal cancer (CRC) carcinogenesis. Due to their stability and accessibility, circulating miRNAs represent a new family of biomarkers with great potential. Therefore, certain miRNAs can be used as diagnostic biomarkers in CRC. Objective: This systematic analysis aimed to explore the individual efficacy of the most investigated blood-based miRNAs for CRC diagnosis, namely miR-21, miR-29a and miR-92a. Methods: Articles were retrieved from databases such as PubMed and Google Scholar, and studies designed to evaluate the diagnostic value of microRNAs in CRC were then selected. We subsequently explored the diagnostic accuracy of each miRNA using parameters such as (SE, SPE, PLR, NLR). The meta-analysis was performed using the Review Manager (Revman) 5.4 software and the Meta Disc software. Results: Our results suggested that serum miR-21 levels showed great potential as a diagnostic molecular marker. The overall pooled results for sensitivity, specificity, area under the curve (AUC), PLR, and NLR were 78%, 91%, 0.9519, 8.12 and 0.17 respectively. Conclusion: miRNAs have become increasingly important in the diagnosis of CRC. Based on these findings, circulating miR-21 levels may have a potential value for early detection and might be used as a novel diagnostic biomarker for CRC.

The intricate cross-talks between tumor cells and their microenvironment play a key role in cancer progression and resistance to treatment. In recent years, targeting pro-tumorigenic components of the tumor microenvironment (TME) has emerged as a tantalizing strategy to improve the efficacy of standard-of-care (SOC) treatments, particularly for hard-to-treat cancers such as glioblastoma. In this review, we explore how the distinct microenvironmental niches characteristic of the glioblastoma TME shape response to therapy. In particular, we delve into the interplay between tumor-associated macrophages (TAM) and glioblastoma cells within angiogenic and hypoxic niches, and interrogate their dynamic co-evolution upon SOC therapies that fuels malignancy. Resolving the complexity of therapy-induced alterations in the glioblastoma TME and their impact on disease relapse is a stepping stone to identify targetable pro-tumorigenic pathways and TAM subsets, and may open the way to efficient combination therapies that will improve clinical outcomes.

Defining clinically relevant MET amplification levels in non-small cell lung cancer (NSCLC) remains challenging. We hypothesize that oncogene overlap and MET amplicon size decline with increase in MET plasma copy number (pCN), thus enriching for MET-dependent states.We interrogated cell-free DNA NGS results of 16,782 patients with newly diagnosed advanced NSCLC to identify those with MET amplification as reported using Guardant360. Co-occurring genomic mutations and copy number alterations within each sample were evaluated. An exploratory method of adjusting for tumor fraction was also performed and amplicon size for MET was analyzed when available.MET amplification was detected in 207 (1.2%) of samples. pCN ranged from 2.1 to 52.9. Of these, 43 (20.8%) had an overlapping oncogenic driver, including 23 (11.1%) METex14 skipping or other MET mutations. The degree of (non-MET) oncogene overlap decreased with increases in pCN. Patients with MET pCN ≥ 2.7 had lower rates of overlapping drivers compared to those with MET pCN2.7 (6.1% vs. 16.3%, P = .033). None of the 7 patients with pCN6.7 had an overlapping driver. After adjusting for tumor fraction, adjusted pCN (ApCN) was also lower for those with overlapping drivers than those without (median ApCN 4.9 vs. 7.3, P =.024). There was an inverse relationship between amplicon size and pCN.We propose that a high MET pCN and/or ApCN, together with the absence of overlapping oncogenic drivers and small MET amplicon size, will enrich for patients most likely to derive benefit from MET targeted therapy.

Despite rapid development of anti-tumorigenic treatments, the clinical outcome for hepatocellular carcinoma (HCC) is still far from satisfactory. With a deeper understanding about tumor microenvironment (TME), the critical role of extracellular vesicles (EVs) as intercellular liaison has come into spotlight. The dynamic functionality of these nanoparticles revealed cancer cells can employ both tumor and non-tumorous components for their own benefit, so as to mediate cell-to-cell communication and interchange of oncogenic biomolecules. Increasing studies on HCC-derived EVs have identified various irregulated biomolecules, that may serve as biomarkers or therapeutic targets. In this review, we first introduce the current knowledge about EVs and how they operate to maintain a healthy liver microenvironment. We then summarize some of the aberrant observations reported on HCC-derived EVs and how they contribute to HCC pathogenesis. Finally, we describe how current treatments for HCC alter behavior of EVs, which may shed light for potential prognostic markers and therapeutic strategies.

Until recently, bacteria have been studied in terms of their roles in infectious diseases and mainly by using isolation and culture methods. However, in practice, many bacteria existing on the earth are difficult to isolate and culture, and thus only a limited number of them have been studied to date. On the other hand, in 2005, the next-generation sequencing technology became generally available, and since then genomic analysis of bacterial flora has become widespread. As a result, it has been revealed that the lower respiratory tract, which was previously thought to be sterile, in fact has bacterial flora (a microbiome) with a high level of biodiversity. In addition, it has been found that various diseases develop and worsen depending on the balance of the bacterial flora, and in recent years, a relationship has been established between various disorders. Recent research on cancer-associated microbial communities has elucidated the reciprocal interactions among bacteria, tumors and immune cells, the bacterial pathways associated with induction of oncogenesis, and their translational significance. Nevertheless, despite the increasing evidence showing that dysbiosis is associated with lung oncogenesis, the detailed mechanisms remain to be fully elucidated. Microorganisms seem to trigger tumor initiation and progression, presumably through the production of bacterio-toxins and other pro-inflammatory factors. The purpose of this review is to present a context for the basic mechanisms and molecular functions of the airway microbiome in oncogenesis, in an effort to prevent cancer by strategies utilizing the airway microbiota, as well as summarizing the mechanisms wherein the microbiome acts as a modulator of immunotherapies in lung cancer.

The active role of bacteria in oncogenesis has long been a topic of debate. Although, it was speculated to be a transmissible cause of cancer as early as the 16th-century, yet the idea about the direct involvement of bacteria in cancer development has only been explored in recent decades. More recently, several studies have uncovered the mechanisms behind the carcinogenic potential of bacteria which are inflammation, immune evasion, pro-carcinogenic metabolite production, DNA damage and genomic instability. On the other side, the recent development on the understanding of tumor microenvironment and technological advancements has turned this enemy into an ally. Studies using bacteria for cancer treatment and detection have shown noticeable effects. Therapeutic abilities of bioengineered live bacteria such as high specificity, selective cytotoxicity to cancer cells, responsiveness to external signals and control after ingestion have helped to overcome the challenges faced by conventional cancer therapies and highlighted the bacterial based therapy as an ideal approach for cancer treatment. In this review, we have made an effort to compile substantial evidence to support the multidimensional role of bacteria in cancer. We have discussed the multifaceted role of bacteria in cancer by highlighting the wide impact of bacteria on different cancer types, their mechanisms of actions in inducing carcinogenicity, followed by the diagnostic and therapeutic potential of bacteria in cancers. Moreover, we have also highlighted the existing gaps in the knowledge of the association between bacteria and cancer as well as the limitation and advantage of bacteria-based therapies in cancer. A better understanding of these multidimensional roles of bacteria in cancer can open up the new doorways to develop early detection strategies, prevent cancer, and develop therapeutic tactics to cure this devastating disease.

Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first‐class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for ‘cross-talk’ between H. pylori and these cells will provide promising strategies for developing new treatments.

Abstract Lung cancer (LC), one of the most common malignant neoplasms, is the leading cause of high cancer mortality worldwide. Smoking is a risk factor for almost all histological types of LC. Benzo[a]pyrene (BaP), one of the main constituents of tobacco smoke, can cause cancer. It has been established that its toxic effects can develop in the following ways: genotoxic (formation of adducts with DNA) and non-genotoxic or epigenetic. The latter is less known, although it is known that BaP activates aryl hydrocarbon receptor (AhR), which regulate transcription of many target genes, including microRNAs, which can lead to initiation and enhancement of the malignant cell transformation. Recent studies are evaluating the role of AhR in the regulation of immune checkpoints, as cigarette smoke and BaP induce the AhR-regulated expression of PD-L1 (CD274) in lung epithelial cells in vitro and in vivo. In addition, kynurenine (a metabolite of tryptophan) has been found to stimulate the PD-1 (CD279) expression in cytotoxic T cells by activating AhR. Recent studies confirm great importance of AhR expressed in malignant cells for suppression of antitumor immunity. All this makes us rethink the role of AhR in lung carcinogenesis and investigate the mechanisms of its activation by exogenous and endogenous ligands. This review highlights the current understanding of the functional features of AhR and its role in the LC pathogenesis.

The chaperonins CCT and Hsp60 are molecular chaperones, members of the chaperone system (CS). Chaperones are cytoprotective but if abnormal in quantity or quality they may cause diseases, the chaperonopathies. Here, recent advances in the understanding of CCT and Hsp60 in cancerology are briefly discussed, focusing on breast and brain cancers. CCT subunits, particularly CCT2, were increased in breast cancer cells and this correlated with tumor progression. Experimental induction of CCT2 increase was accompanied by an increase of CCT3, 4, and 5, providing another evidence for the interconnection between the members of the CS and the difficulties expected while manipulating one member with therapeutic purposes. Another in silico study demonstrated a direct correlation between the increase in the tumor tissue of the mRNA levels of all CCT subunits, except CCTB6, with bad prognosis. Studies with glioblastomas demonstrated an increase in the CCT subunits in the tumor tissue and in extracellular vesicles (EVs) derived from them. Expression levels of CCT1, 2, 6A, and 7 were the most increased and markers of bad prognosis, particularly CCT6A. A method for measuring Hsp60 and related miRNA in exosomes from blood of patients with glioblastomas or other brain tumors was discussed, and the results indicate that the triad Hsp60-related miRNAs-exosomes has potential regarding diagnosis and patient monitoring. All these data provide a strong foundation for future studies on the role played by chaperonins in carcinogenesis and for fully developing their theranostics applications along with exosomes.

The receptor tyrosine kinase EPHB2 (EPH receptor B2) is highly expressed in many human cancer types, especially in gastrointestinal cancers, such as colorectal cancer. Several coding mutations of the EPHB2 gene have been identified in many cancer types, suggesting that EPHB2 plays a critical role in carcinogenesis. However, the exact functional mechanism of EPHB2 in carcinogenesis remains unknown. In this study, we find that EPHB2 is required for TNF-induced signaling activation and proinflammatory cytokine production in colorectal epithelial cells. Mechanistically, after TNF stimulation, EPHB2 is ubiquitinated by its E3 ligase RNF186. Then, ubiquitinated EPHB2 recruits and further phosphorylates TAB2 at nine tyrosine sites, which is a critical step for the binding between TAB2 and TAK1. Due to defects in TNF signaling in RNF186-knockout colorectal epithelial cells, the phenotype of colitis-propelled colorectal cancer model in RNF186-knockout mice is significantly reduced compared with that in wild-type control mice. Moreover, we find that a genetic mutation in EPHB2 identified in a family with colorectal cancer is a gain-of-function mutation that promoted TNF signaling activation compared with wild-type EPHB2. We provide evidence that the EPHB2-RNF186-TAB2-TAK1 signaling cascade plays an essential role in TNF-mediated signal transduction in colorectal epithelial cells and the carcinogenesis of colorectal cancer, which may provide potential targets for the treatment of colorectal cancer.

Alterations in metabolic pathways are a hallmark of cancer. A deeper understanding of the contribution of different metabolites to carcinogenesis is thus vitally important to elucidate mechanisms of tumor initiation and progression to inform therapeutic strategies. Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide and its altered metabolic landscape is beginning to unfold with the advancement of technologies. In particular, characterization of the lipidome of human HCCs has accelerated, and together with biochemical analyses, are revealing recurrent patterns of alterations in glycerophospholipid, sphingolipid, cholesterol and bile acid metabolism. These widespread alterations encompass a myriad of lipid species with numerous roles affecting multiple hallmarks of cancer, including aberrant growth signaling, metastasis, evasion of cell death and immunosuppression. In this review, we summarize the current trends and findings of the altered lipidomic landscape of HCC and discuss their potential biological significance for hepatocarcinogenesis.

Pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) consists of multiple cell types interspersed by dense fibrous stroma. These cells communicate through low molecular weight signaling molecules called cytokines. The cytokines, through their receptors, facilitate PDAC initiation, progression, metastasis, and distant colonization of malignant cells. These signaling mediators secreted from tumor-associated macrophages, and cancer-associated fibroblasts in conjunction with oncogenic Kras mutation initiate acinar to ductal metaplasia (ADM), resulting in the appearance of early preneoplastic lesions. Further, M1- and M2-polarized macrophages provide proinflammatory conditions and promote deposition of extracellular matrix, whereas myofibroblasts and T-lymphocytes, such as Th17 and T-regulatory cells, create a fibroinflammatory and immunosuppressive environment with a significantly reduced cytotoxic T-cell population. During PDAC progression, cytokines regulate the expression of various oncogenic regulators such as NFκB, c-myc, growth factor receptors, and mucins resulting in the formation of high-grade PanIN lesions, epithelial to mesenchymal transition, invasion, and extravasation of malignant cells, and metastasis. During metastasis, PDAC cells colonize at the premetastatic niche created in the liver, and lung, an organotropic function primarily executed by cytokines in circulation or loaded in the exosomes from the primary tumor cells. The indispensable contribution of these cytokines at every stage of PDAC tumorigenesis makes them exciting candidates in combination with immune-, chemo- and targeted radiation therapy.