353 results on '"Author’s Views"'
Search Results
2. Targeting cancer's sweet spot: UGP2 as a therapeutic vulnerability
- Author
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Andrew Wolfe, Sung Eun Kim, and Sung-Hoon Kim
- Subjects
Cancer Research ,Sweet spot ,UDP Glucose ,Metabolic reprogramming ,Vulnerability ,Cancer ,Computational biology ,Biology ,medicine.disease ,Cancer metabolism ,Cancer cell ,medicine ,Author’s Views ,Molecular Medicine - Abstract
Understanding the mechanisms governing metabolic reprogramming that underlie potential vulnerabilities in cancer cells is key to developing novel therapeutic strategies. The catalytic enzyme UDP-glucose pyrophosphorylase 2 (UGP2) drives the production of UDP-glucose. Our recent work demonstrated the crucial role of UGP2 in cancer growth and its regulation of cellular metabolic processes.
- Published
- 2022
3. SPF45/RBM17-dependent splicing and multidrug resistance to cancer chemotherapy
- Author
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Akila Mayeda, Julian P. Venables, and Kazuhiro Fukumura
- Subjects
Multiple drug resistance ,Cancer Research ,Cancer chemotherapy ,RNA splicing ,Cancer research ,Author’s Views ,Molecular Medicine ,Biology - Abstract
The early splicing complex A occupies at least eighty nucleotides of intron, in which U2AF covers the polypyrimidine tract. SPF45 (RBM17) functionally substitutes for U2AF on a subset of short introns. Since SPF45 expression confers resistance to various anticancer drugs, SPF45-dependent splicing may play a critical role in multidrug resistance.
- Published
- 2022
4. Cell demise inhibited: Unexpected liaisons between mitochondria and IκΒα
- Author
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Evangelos Pazarentzos
- Subjects
Cancer Research ,Cell ,NFKBIA Gene ,Mitochondrion ,Biology ,Cell biology ,Voltage-Dependent Anion Channel 1 ,medicine.anatomical_structure ,Apoptosis ,medicine ,Author’s Views ,Molecular Medicine ,Bacterial outer membrane ,Transcription factor ,VDAC1 - Abstract
IκΒα (the protein product of NFKBIA gene) has widely been considered a pro-apoptotic factor due to its ability to inhibit the anti-apoptotic transcription factor NFκB. Our findings indicate that IκΒα also exerts a strong anti-apoptotic activity at the outer mitochondria membrane (OMM). This function we uncovered is distinct from its ability to sequester and inhibit NFκB. IκΒα instead binds to voltage dependent anion channel 1 (VDAC1) and Hexokinase 2 (HK2), stabilizes this complex and prevents mitochondria outer membrane permeabilisation (MOMP) and apoptosis.
- Published
- 2022
5. Tumor suppressor pathways shape EGFR-driven lung tumor progression and response to treatment
- Author
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Giorgia Foggetti, Chuan Li, Hongchen Cai, Dmitri A. Petrov, Monte M. Winslow, and Katerina Politi
- Subjects
Cancer Research ,multiplexed in vivo genome editing ,EGFR ,Lung Cancer ,Human Genome ,targeted therapy ,Rare Diseases ,Author’s Views ,Genetics ,Molecular Medicine ,2.1 Biological and endogenous factors ,tumor suppressor genes ,Aetiology ,Lung ,Cancer - Abstract
In vivo modeling combined with CRISPR/Cas9-mediated somatic genome editing has contributed to elucidating the functional importance of specific genetic alterations in human tumors. Our recent work uncovered tumor suppressor pathways that affect EGFR-driven lung tumor growth and sensitivity to tyrosine kinase inhibitors and reflect the mutational landscape and treatment outcomes in the human disease.
- Published
- 2022
6. Aurora A and Mcl-1: new potential treatment targets in antiestrogen-resistant breast cancer
- Author
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Christina W Yde
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Myeloid ,Fulvestrant ,business.industry ,Cell ,medicine.disease ,Antiestrogen ,Leukemia ,Biomarker ,Breast cancer ,medicine.anatomical_structure ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Author’s Views ,Molecular Medicine ,business ,skin and connective tissue diseases ,Tamoxifen ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Antiestrogen resistance is a major clinical limitation in treatment of breast cancer. We have recently reported that Aurora A and Mcl-1 (myeloid cell leukemia 1) are potential novel treatment targets in antiestrogen-resistant breast cancer cells and that Aurora A expression is a biomarker for tamoxifen resistance in breast cancer patients. Abbreviations: Bcl-2, B-cell lymphoma 2; EGF, epidermal growth factor; ERα, estrogen receptor α; Mcl-1, myeloid cell leukemia 1; VEGF, vascular endothelial growth factor.
- Published
- 2021
7. CTCF puts a new twist on UV damage and repair in skin cancer
- Author
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Bastian Stark, Gregory M. K. Poon, and John J. Wyrick
- Subjects
Cancer Research ,Author’s Views ,Molecular Medicine - Abstract
Somatic mutations in skin cancers are highly enriched at binding sites for CCCTC-binding factor (CTCF). We have discovered that CTCF binding alters the DNA structure to render it more susceptible to UV damage. Elevated UV damage formation at CTCF binding sites, in conjunction with subsequent repair inhibition, promotes UV mutagenesis.
- Published
- 2021
8. Targeting the immune microenvironment during immunotherapy for solid tumors
- Author
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Aiman Sabaawy and Saman Zeeshan
- Subjects
Cancer Research ,Tumor microenvironment ,business.industry ,Immune microenvironment ,medicine.medical_treatment ,JAK-STAT signaling pathway ,Immunotherapy ,stat ,Immunosurveillance ,Immune system ,Cancer research ,Author’s Views ,Molecular Medicine ,Medicine ,Stat signaling ,business - Abstract
JAK/STAT signaling is a central hub in cancer development, progression, immunosurveillance and response to immunotherapy. We discuss recent advances in the role of the JAK/STAT pathway in immunotherapies. We stress the importance of fully understanding how JAK/STAT modifies the immune response before implementing clinical trials combining JAK/STAT inhibitors with immunotherapy.
- Published
- 2021
9. Simplifying cancer: binary pan-cancer superclasses stratified by opposite YAP/TEAD effects
- Author
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Joel Pearson and Rod Bremner
- Subjects
0303 health sciences ,Cancer Research ,Pan cancer ,TAZ/WWTR1 ,Neuroendocrine Cancer ,leukemia ,Cancer ,Treatment options ,Biology ,medicine.disease ,3. Good health ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,neuroendocrine cancer ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Author’s Views ,Molecular Medicine ,Cancer biology ,YAP ,small cell lung cancer ,030304 developmental biology ,Article Commentary - Abstract
The inherent complexity of cancer complicates treatment. Identifying higher-order principles that govern cancer biology can circumvent this problem and pinpoint broadly applicable treatment options. We recently found that opposite expression and pro- versus anti-cancer activity of a single transcriptional complex functionally stratifies cancer into binary superclasses.
- Published
- 2021
10. Mitochondrial homeostasis is maintained in the absence of autophagy
- Author
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Christina G. Towers
- Subjects
Cancer Research ,Chemistry ,Vesicle ,Autophagy ,Cancer ,Mitochondrion ,medicine.disease ,Cell biology ,Cancer cell ,Mitophagy ,medicine ,Author’s Views ,Molecular Medicine ,Mitochondrial homeostasis - Abstract
Autophagy is a central recycling process, and it plays a complex role in cancer. We discovered that when autophagy is blocked, cancer cells compensate by increasing mitochondrial-derived vesicles. However, there are many unanswered questions remaining, particularly in the context of the dual roles of autophagy in cancer.
- Published
- 2021
11. Mitotic WNT: aligning chromosomes through KIF2A
- Author
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Anja Bufe and Sergio P. Acebrón
- Subjects
Cancer Research ,Author’s Views ,Molecular Medicine - Abstract
WNT signaling regulates cell cycle progression and fate determination through β-catenin dependent transcription, and its misregulation is often associated with tumorigenesis. Our recent work demonstrated that basal WNT activity is also required to ensure proper chromosome alignment during mitosis through the regulation of kinesin family member 2A (KIF2A).
- Published
- 2021
12. Novel insights into the RTK-dependent metastatic phenotype of KRAS-mutant lung adenocarcinoma
- Author
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Mariana Cooke
- Subjects
Cancer Research ,Author’s Views ,Molecular Medicine - Abstract
In a recent study, our group identified RAC guanine nucleotide exchange factors (RAC-GEFs) driving motility signaling in KRAS mutant lung adenocarcinoma cells. The RAC-GEFs FARP1, ARHGEF39 and TIAM2 play fundamental roles in the formation of membrane ruffles in response to growth factor receptor stimulation.
- Published
- 2021
13. Interdisciplinary team science to understand and intercept rare cancers
- Author
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Stefan Fröhling
- Subjects
Cancer Research ,Medical education ,Author’s Views ,Molecular Medicine ,Psychology ,Team science - Abstract
For most rare cancers, precision oncology approaches are not established because these entities are poorly understood and their investigation requires the collaboration of many centers. The MASTER precision oncology network demonstrates that clinical whole-genome/exome and RNA sequencing yield molecular mechanism-aware treatments that benefit a substantial proportion of patients with advanced rare cancers and will prepare the ground for future clinical trials.
- Published
- 2021
14. The concerted action of oncogenic driver mutations directs global translation in intestinal epithelial cells
- Author
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Jarom Heijmans, Wouter L. Smit, Graduate School, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, General Internal Medicine, and Clinical Haematology
- Subjects
Cancer Research ,Messenger RNA ,driver mutations ,protein synthesis ,Colorectal cancer ,Translation (biology) ,Biology ,medicine.disease_cause ,medicine.disease ,Cell biology ,Transformation (genetics) ,Organoid ,medicine ,Protein biosynthesis ,mTOR signaling ,Author’s Views ,Molecular Medicine ,KRAS ,Enhancer ,neoplasms ,global translation - Abstract
Oncogenic transformation of colorectal cancer cells is driven by a set of mutations that cause aberrant signaling of growth factor–receptor pathways. Using organoids, we demonstrate that the most frequent driver mutations in APC, KRAS, SMAD4, and TP53 are enhancers of the global mRNA translational capacity, which is linked to intestinal cell growth in an mTOR-dependent manner.
- Published
- 2021
15. Hydrogen sulfide operates as a glioblastoma suppressor and is lost under high fat diet
- Author
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Christopher Hine, Justin D. Lathia, and Daniel J. Silver
- Subjects
Cancer Research ,urogenital system ,High fat diet ,Transsulfuration ,Biology ,urologic and male genital diseases ,medicine.disease ,Phenotype ,nervous system diseases ,law.invention ,Cancer stem cell ,In vivo ,law ,Western diet ,Cancer research ,medicine ,Author’s Views ,Molecular Medicine ,Suppressor ,Glioblastoma - Abstract
Glioblastoma (GBM) is one of the deadliest and aggressive forms of brain cancer. Environmental and intrinsic factors such as Western Diet and advanced age can function as powerful accelerants to the progression of GBM. Recently, we discovered that pre-clinical GBM models subject to an obesogenic and age-accelerating high fat diet (HFD) presented with hyperaggressive GBM phenotypes, including treatment-refractory cancer stem cell (CSC) enrichment. Mechanistically, HFD suppressed production of the gasotransmitter hydrogen sulfide (H(2)S) and its downstream sulfhydration signaling in the brain. Likewise, we observed dramatic loss of sulfhydration in brains of GBM patients. Importantly, we showed the tumor suppressive effects of H(2)S against GBM in cell culture and in vivo. Here, we discuss these recent findings and provide insight into how they can be leveraged to improve treatment modalities, prognosis, and quality of life for GBM patients.
- Published
- 2021
16. SGK1-regulated metabolism: key for the survival of cells detached from the extracellular matrix
- Author
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Zachary T. Schafer and Jordan A. Cockfield
- Subjects
chemistry.chemical_classification ,Cancer Research ,Reactive oxygen species ,Metabolism ,Pentose phosphate pathway ,Cell biology ,Small hairpin RNA ,Extracellular matrix ,chemistry ,medicine ,Author’s Views ,Molecular Medicine ,Anoikis ,Signal transduction ,Glucocorticoid ,medicine.drug - Abstract
Cells that lack attachment to the extracellular matrix (ECM) experience metabolic defects that can lead to caspase-independent cell death. Recently, we discovered that serum and glucocorticoid kinase-1 (SGK1) plays a critical role in the regulation of glucose metabolism, the promotion of energy production, and ultimately the survival of ECM-detached cells. Abbreviations: ECM, extracellular matrix; SGK1, serum and glucocorticoid kinase-1; ROS, reactive oxygen species; CCCP, cyanide m-chlorophenyl hydrazine; PPP, pentose phosphate pathway; G3P, glyceraldhyde-3-phosphate; shRNA, short hairpin RNA; TCA, tricarboxylic acid.
- Published
- 2021
17. Deciphering the modes of human separase inhibition by securin and CDK1-CCNB1
- Author
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Andreas Boland, Jun Yu, and Pierre Raia
- Subjects
0303 health sciences ,Cancer Research ,Cyclin-dependent kinase 1 ,Cohesin ,Cohesin complex ,Chemistry ,Cell biology ,Chromosome segregation ,03 medical and health sciences ,0302 clinical medicine ,Securin ,030220 oncology & carcinogenesis ,Author’s Views ,Molecular Medicine ,Sister chromatids ,biological phenomena, cell phenomena, and immunity ,Separase ,Mitosis ,030304 developmental biology - Abstract
Accurate chromosome segregation depends on tight regulation of the protease separase, which cleaves the ring-shaped cohesin complex that entraps the two sister chromatids. We recently reported structures of human separase bound to its inhibitors securin or the cyclin-dependent kinase 1 (CDK1)-cyclin B1 (CCNB1)-cyclin-dependent kinases regulatory subunit 1 (CKS1) complex and discovered an array of molecular mechanisms that block cohesin-cleavage.
- Published
- 2021
18. KMT2D deficiency confers a therapeutic vulnerability to glycolytic and IGFR inhibitors in melanoma
- Author
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Mayinuer Maitituoheti and Navya Murugesan
- Subjects
Cancer Research ,enhancer reprogramming ,Methyltransferase ,biology ,business.industry ,KMT2D ,glycolysis ,Histone H3 ,Metabolic pathway ,Histone ,Growth factor receptor ,RNA interference ,Author’s Views ,melanoma ,Cancer research ,biology.protein ,Molecular Medicine ,Medicine ,Glycolysis ,business ,Article Commentary ,Insulin-like growth factor 1 receptor - Abstract
We reported that histone H3 lysine (K) 4 methyltransferase, KMT2D, serves as a potent tumor-suppressor in melanoma, which was identified via in vivo epigenome-focused RNA interference (RNAi) screen. KMT2D-deficient tumors show substantial reprogramming of key metabolic pathways including glycolysis via reduction of H3K4me1 (Histone H3K4 mono-methylation)-marked active enhancers, conferring sensitivity to inhibitors of glycolysis and IGFR (Insulin Growth Factor Receptor) pathway.
- Published
- 2021
19. How multi-component cascades operate in cells: lessons from the ubiquitin system-containing liquid-separated condensates
- Author
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Victoria Cohen-Kaplan, Afu Fu, Ido Livneh, and Aaron Ciechanover
- Subjects
Cancer Research ,Ubiquitin ,biology ,Chemistry ,Component (UML) ,Author’s Views ,biology.protein ,Molecular Medicine ,Nanotechnology ,Protein degradation - Abstract
Membraneless condensates have recently caught the attention of biologists as hubs for cellular components required for catalysis of basic processes. Whether they are real has become the center of heated discussion where the main issues are their mechanism of assembly and function. A recent study describing these condensates as hubs for protein degradation by the ubiquitin system may shed a new light on this recent development in cell biology.
- Published
- 2021
20. Epigenetic condensates regulate chromatin activity and tumorigenesis
- Author
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Bi Shi, Wei Li, and Hao Jiang
- Subjects
Cancer Research ,Methyltransferase ,biology ,Lysine ,Phase separation ,Cancer ,condensates ,medicine.disease_cause ,medicine.disease ,complex mixtures ,Cell biology ,Chromatin ,UTX ,Author’s Views ,medicine ,biology.protein ,chromatin ,bacteria ,Molecular Medicine ,Demethylase ,KDM6A ,Epigenetics ,Carcinogenesis ,epigenetic ,Article Commentary - Abstract
Alterations of epigenetic modulators are extensively associated with cancer, but their key molecular activities in cancer regulation are often unclear. We discovered that lysine demethylase 6A (KDM6A, also known as UTX) suppresses cancer by forming liquid-like condensates with lysine methyltransferase 2D (KMT2D, also known as MLL4) and regulating chromatin activity at multiple levels.
- Published
- 2021
21. From mouse genetics to targeting the Rag GTPase pathway
- Author
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Ortega-Molina, Ana and Efeyan, Alejo
- Subjects
Cancer Research ,Human disease ,Author’s Views ,biology.protein ,Molecular Medicine ,Identification (biology) ,GTPase ,Biology ,Small molecule ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,Cell biology - Abstract
The identification of the Rag GTPases initiated the deciphering of the molecular puzzle of nutrient signaling to the mechanistic target of rapamycin (mTOR), and spurred interest in targeting this pathway to combat human disease. Recent mouse genetic studies have provided pathophysiological insight and pointed to potential indications for inhibitors of the Rag GTPase pathway.
- Published
- 2021
22. A scientific journey from discovery to validation of efficacy in cancer patients: HAMLET and alpha1-oleate
- Author
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Marek Babjuk, Ines Ambite, Kenneth Hun Mok, Catharina Svanborg, and James C. S. Ho
- Subjects
Cancer Research ,Novel cancer therapy ,Tumor cells ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,protein folding ,medicine ,Author’s Views ,low toxicity ,030304 developmental biology ,Molecular entity ,0303 health sciences ,Bladder cancer ,Low toxicity ,business.industry ,Cancer ,medicine.disease ,3. Good health ,Clinical trial ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,bladder cancer ,HAMLET (protein complex) ,peptide-oleate complex ,business ,Research Article - Abstract
The protein-lipid complex alpha1-oleate, derived from HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), is identified as a molecular entity with significant therapeutic potential. Structural characterization of the complex and results of a successful placebo-controlled clinical trial are presented.
- Published
- 2021
23. BNIP3 in melanoma: isn’t it IRONic?
- Author
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Monica Vara-Perez and Patrizia Agostinis
- Subjects
Cancer Research ,Activator (genetics) ,Melanoma ,Autophagy ,Hypoxia (medical) ,Biology ,medicine.disease ,Lymphoma ,Hypoxia-Inducible Factor 1-Alpha ,Nuclear receptor ,Mitophagy ,medicine ,Cancer research ,Author’s Views ,Molecular Medicine ,medicine.symptom - Abstract
Melanoma cells exploit mitophagy and hypoxia signaling to promote their growth. In a recent study, we found that loss of B-cell lymphoma 2 (BCL-2)/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3) curbed Hypoxia Inducible Factor 1 alpha (HIF-1α) levels and melanoma growth in vivo. Insufficient levels of BNIP3 boost iron-driven prolyl hydroxylase 2 (Phd2)-mediated degradation of HIF-1α by exacerbating nuclear receptor activator 4 (Ncoa4)-mediated ferritinophagy. Thus, BNIP3 promotes melanoma growth by controlling iron metabolism.
- Published
- 2021
24. AMBRA1 and FAK1: crosstalking for improved targeted therapy in melanoma
- Author
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Luca Di Leo and Daniela De Zio
- Subjects
Cancer Research ,Melanoma ,medicine.medical_treatment ,Protein phosphatase 2 ,Biology ,medicine.disease ,Targeted therapy ,Focal adhesion ,Cutaneous melanoma ,medicine ,Cancer research ,biology.protein ,Author’s Views ,Molecular Medicine ,Tensin ,PTEN ,neoplasms ,Protein kinase B - Abstract
Through genetically engineered mouse models of melanoma, we identified Autophagy/beclin 1 regulator 1 (Ambra1) as novel tumor-suppressor in melanoma. In these settings, loss of Ambra1 associated with the hyperactivation of focal adhesion kinase 1 (Fak1) signaling, the inhibition of which resulted in reduced tumor growth and invasiveness. We therefore propose FAK1 inhibition for current melanoma therapy in AMBRA1-low tumors. Abbreviations AKT, serine/threonine kinase 1; AMBRA1, autophagy/beclin 1 regulator 1; BRAF, v-raf murine sarcoma viral oncogene homolog; BRAFi, BRAF inhibitor; CCLE, Cancer Cell Line Encyclopedia;g ESTDAB, European Searchable Tumor Line Database; FAK1, focal adhesion kinase 1; FAKi, FAK1 inhibitor; LMC, Leeds Melanoma Cohort; MEK, MAPK/ERK kinase; PP2A, protein phosphatase 2A; PTEN, phosphatase and tensin homolog; TCGA-SKCM, The Cancer Genome Atlas - Skin Cutaneous Melanoma; YAP, yes-associated protein 1.
- Published
- 2021
25. Predicting survival of cancer patients by chromosomal copy number heterogeneity
- Author
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Daniël M. Miedema, Louis Vermeulen, Erik van Dijk, Tom van den Bosch, Center of Experimental and Molecular Medicine, Graduate School, CCA - Cancer biology and immunology, Amsterdam Gastroenterology Endocrinology Metabolism, Oncology, and CCA - Imaging and biomarkers
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,chromosomal instability ,Pan cancer ,business.industry ,pan-cancer ,intra-tumor heterogeneity ,Cancer ,Biomarker ,Single copy ,medicine.disease ,Chromosome instability ,Internal medicine ,Author’s Views ,medicine ,Molecular Medicine ,Biomarker (medicine) ,Clinical significance ,business ,Article Commentary - Abstract
We recently introduced a method to derive intra-tumor heterogeneity (ITH) from a single copy number measurement. This method stratifies patients for survival and could potentially help to identify low and high-risk patients with clinical relevance.
- Published
- 2021
26. Non-neuroendocrine differentiation generates a ferroptosis-prone lipidome in small cell lung cancer (SCLC)
- Author
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Christina M. Bebber and Silvia von Karstedt
- Subjects
Cancer Research ,Programmed cell death ,GPX4 ,Neuroendocrine differentiation ,Lipid peroxidation ,chemistry.chemical_compound ,Downregulation and upregulation ,Author’s Views ,GSH ,Ferroptosis ,ether lipids ,neoplasms ,SCLC ,lipid peroxidation ,thioredoxin ,Glutathione ,Lipidome ,humanities ,respiratory tract diseases ,cell death ,neuroendocrine cancer ,chemistry ,Cancer research ,Molecular Medicine ,Thioredoxin ,PUFA ,Article Commentary - Abstract
Our recent study revealed that non-neuroendocrine small cell lung cancer (SCLC) is sensitive to the induction of ferroptosis due to upregulation of ether lipid synthesis. While neuroendocrine SCLC is ferroptosis resistant, it acquires addiction to the thioredoxin pathway. Combined redox pathway targeting therefore achieves efficient anti-tumor activity in heterogenous SCLC.
- Published
- 2021
27. Regulation of glycolysis and cancer cell proliferation by PKM2 citrullination
- Author
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Sebastien Coassolo, Irwin Davidson, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Davidson, Irwin
- Subjects
Cancer Research ,Allosteric regulation ,PKM2 ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Citrulline ,Author’s Views ,melanoma ,030304 developmental biology ,0303 health sciences ,010405 organic chemistry ,protein arginine deiminase ,Citrullination ,Protein-arginine deiminase ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,allosteric regulation ,0104 chemical sciences ,Biochemistry ,chemistry ,PADI1 ,PADI3 ,Molecular Medicine ,chromatin ,Pyruvate kinase - Abstract
International audience; Conversion of peptidyl-arginine to peptidyl citrulline, known as citrullination, is a posttranslational protein modification catalysed by the PADI (Protein Arginine Deiminase) family of enzymes. PADI1 and PADI3 catalyse citrullination of arginine 106 in the glycolytic enzyme pyruvate kinase M2 modulating its allosteric regulation, glycolysis and cancer cell proliferation.
- Published
- 2021
28. A late endosome signaling hub that couples PI3Kα and WNT/β-catenin signaling in breast cancer
- Author
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Lisa M Ooms, Samuel J. Rodgers, Christina Anne Mitchell, and Sabryn A. Hamila
- Subjects
Cancer Research ,medicine.drug_class ,Cell growth ,Effector ,Biology ,P110α ,medicine.disease ,Breast cancer ,Estrogen ,Author’s Views ,medicine ,Cancer research ,Molecular Medicine ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Late endosome - Abstract
AKT is the central phosphoinositide 3-kinase (PI3K) signaling effector, however, PIK3CA (p110α subunit of PI3Kα)-mutant estrogen receptor-positive (ER(+)) breast cancers exhibit minimal AKT activation and the downstream signaling is poorly characterized. We discovered that a subset of PIK3CA-mutant ER(+) breast cancers exhibit increased inositol polyphosphate 4-phosphatase type II (INPP4B) expression, which promotes late endosome formation and glycogen synthase kinase 3 beta (GSK3β) trafficking, leading to enhanced Wingless–related integration site (WNT)/catenin beta 1 (β-catenin) activation.
- Published
- 2021
29. TFG: a novel regulator of ULK1-dependent autophagy
- Author
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Francesca Nazio and Francesco Cecconi
- Subjects
Omegasome ,Cancer Research ,Settore BIO/06 ,Kinase ,Autophagy ,neurological disorders ,Regulator ,TFG ,omegasome ,Biology ,ULK1 ,ERGIC ,medicine.disease_cause ,Immunoglobulin light chain ,Cell biology ,medicine ,Author’s Views ,Molecular Medicine ,Carcinogenesis ,Gene ,Article Commentary - Abstract
TRK-fused gene (TFG) is a protein implicated in multiple neurodegenerative diseases and oncogenesis. We have recently shown that, under starvation conditions, TFG contributes to spatial control of autophagy by facilitating Unc-51 like autophagy activating kinase 1 (ULK1)-microtubule-associated protein 1 light chain 3 gamma (MAP1LC3C) interaction to modulate omegasome and autophagosome formation. Defective TFG-mediated autophagy could thus be postulated as a possible contributor to ontogenesis or progression of TFG-related diseases.
- Published
- 2021
30. Cancer-associated keratinocytes: new members of the microenvironment in head and neck cancer
- Author
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Erika Danella, Nisha J. D'Silva, and Marcell Costa de Medeiros
- Subjects
Cancer Research ,Tumor microenvironment ,Extracellular proteins ,business.industry ,Mechanism (biology) ,Head and neck cancer ,Cancer ,medicine.disease ,Complex ecosystem ,Metastasis ,Tumor progression ,Author’s Views ,Cancer research ,Molecular Medicine ,Medicine ,business - Abstract
The tumor microenvironment is a complex ecosystem of malignant and nonmalignant cells and extracellular proteins that work together to enhance tumor progression. We identified a mechanism in which adjacent nonmalignant epithelium enhances invasion of squamous cell carcinoma, thereby expanding the tumor microenvironment to include cancer-associated keratinocytes.
- Published
- 2021
31. Novel subtypes of NPM1-mutated AML with distinct outcome
- Author
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Benjamin Haibe-Kains, Arvind Singh Mer, Mark D. Minden, and Aaron D. Schimmer
- Subjects
0303 health sciences ,Cancer Research ,NPM1 ,Myeloid leukemia ,Patient survival ,Disease ,Biology ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Cancer research ,Author’s Views ,Molecular Medicine ,Recurrent mutation ,030304 developmental biology ,030215 immunology - Abstract
Acute myeloid leukemia (AML) is heterogeneous with one common subtype recognized by the presence of recurrent mutation of nucleophosmin-1 (NPM1). Emerging evidence indicates that within NPM1 mutated AML there is variation in outcome which challenges how best to characterize and treat the individual patient. Our recent findings show that there are two distinct (primitive and committed) subtypes within NPM1 mutated AML patients. These subtypes exhibit specific molecular characteristics, disease differentiation states, patient survival, and differential drug responses.
- Published
- 2021
32. Metabolic checkpoint of ferroptosis resistance
- Author
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Daolin Tang, Jiao Liu, and Rui Kang
- Subjects
0301 basic medicine ,Pyruvate decarboxylation ,Cancer Research ,Pyruvate dehydrogenase kinase 4 ,Ferroptosis ,PDK4 ,medicine.disease ,Cell biology ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Downregulation and upregulation ,030220 oncology & carcinogenesis ,Pancreatic cancer ,medicine ,Author’s Views ,Molecular Medicine ,Fatty acid synthesis - Abstract
The metabolic checkpoint of ferroptosis remains obscure. We find that glucose favors system xc(−) inhibitor-induced ferroptosis by activating pyruvate oxidation, thereby promoting fatty acid synthesis and subsequent lipid peroxidation. In contrast, the upregulation of pyruvate dehydrogenase kinase 4 (PDK4) switches into a ferroptosis-resistant state in pancreatic cancer cells.
- Published
- 2021
33. Unlocking p53 response elements: DNA shape is the key
- Author
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Steven B. McMahon and Marina Farkas
- Subjects
0301 basic medicine ,Cancer Research ,Programmed cell death ,Computational biology ,Biology ,Cell fate determination ,Genome ,DNA sequencing ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,law ,Regulatory sequence ,Author’s Views ,Molecular Medicine ,Suppressor ,Gene ,030217 neurology & neurosurgery ,DNA - Abstract
For recognition of specific regulatory sequences in the genome (i.e., response elements, REs), the tumor suppressor protein 53 kDa (p53) exhibits dose-dependent selectivity. In general, binding to REs linked to target genes involved in the positive regulation of cell death requires higher levels of p53 than those connected to cell survival. Our recent findings provide a mechanistic explanation for this phenomenon. Specifically, we demonstrate that subtle differences in DNA shape, encoded in RE DNA sequence, determine the utilization of two biochemically distinct DNA-binding modes, ultimately connected to different biological outcomes.
- Published
- 2021
34. The PIDDosome: centrosome guardian and backup on the DNA damage response
- Author
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Matteo Burigotto and Luca L. Fava
- Subjects
0303 health sciences ,Cancer Research ,DNA damage ,Genotoxic Stress ,Cell fate determination ,Biology ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,Centrosome ,030220 oncology & carcinogenesis ,Organelle ,Author’s Views ,Molecular Medicine ,Ankyrin repeat ,030304 developmental biology ,Death domain - Abstract
The PIDDosome is a Caspase-2-activating platform assembling in response to centrosome amplification or genotoxic stress. We have recently shown that both stimuli depend on ANKRD26 (ankyrin repeat domain-containing protein 26)-mediated localization of PIDD1 (p53-inducible protein with death domain) at the centrosome, demonstrating how this organelle can directly influence cell fate.
- Published
- 2021
35. It takes three to the DNA damage response tango
- Author
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Yael Ziv, Sapir Schlam-Babayov, and Yosef Shiloh
- Subjects
0303 health sciences ,Cancer Research ,congenital, hereditary, and neonatal diseases and abnormalities ,Kinase ,Chemistry ,DNA damage ,medicine.disease ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ataxia-telangiectasia ,medicine ,Author’s Views ,Molecular Medicine ,Protein kinase A ,030217 neurology & neurosurgery ,DNA ,030304 developmental biology - Abstract
The DNA damage response is robustly activated by DNA double-strand breaks and controlled by three apical protein kinases of the PI3-kinase-related protein kinase (PIKK) family: ataxia-telangiectasia, mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK). Phosphoproteomic analysis reveals the relative share of these PIKKs in coordinating this network, and compensation by ATR and DNA-PK for ATM absence in the genetic disorder, ataxia-telangiectasia (A-T).
- Published
- 2021
36. Metabolic subtypes of clear cell renal cell carcinoma defined by tobacco smoking
- Author
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John T. Cunningham, Maria F. Czyzyk-Krzeska, Jarek Meller, Julio A. Landero Figueroa, and David R. Plas
- Subjects
0301 basic medicine ,inorganic chemicals ,Cancer Research ,Chemistry ,Glutamate receptor ,Oxidative phosphorylation ,Metabolism ,medicine.disease ,Glutamine ,03 medical and health sciences ,Clear cell renal cell carcinoma ,Metabolic pathway ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Author’s Views ,Molecular Medicine ,Glycolysis ,Reprogramming - Abstract
Tobacco smoking (TS) results in reprogramming of major metabolic pathways, including glycolysis, the citric acid (TCA) cycle, oxidative phosphorylation, and metabolism of aspartate, glutamate and glutamine in clear cell renal cell carcinoma (ccRCC). TS alters the distribution and activities of cadmium, arsenic and copper in a manner mechanistically supporting metabolic remodeling. Alterations in metabolism and metal distribution identify new actionable targets for treatment of ccRCC.
- Published
- 2021
37. Tuning protein synthesis for cancer therapy
- Author
-
John R. P. Knight and Owen J. Sansom
- Subjects
0301 basic medicine ,Cancer Research ,endocrine system diseases ,Colorectal cancer ,Cancer therapy ,colorectal cancer ,MYC ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Protein biosynthesis ,Author’s Views ,neoplasms ,Total protein ,EIF4E ,KRAS mutation ,Translation (biology) ,medicine.disease ,Activating mutation ,digestive system diseases ,3. Good health ,respiratory tract diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,eIF4E ,Cancer research ,Molecular Medicine ,KRAS ,Protein synthesis ,Article Commentary - Abstract
~50% of colorectal cancers have an activating mutation in KRAS (encoding the KRAS proto-oncogene) and remain difficult to target in the clinic. We have recently shown that activation of KRAS protein alters the regulation of mRNA translation, increasing total protein synthesis, and maintaining elevated c-MYC (MYC proto-oncogene) expression. Targeting these pathways downstream of KRAS reveals a striking dependency that has potential for clinical translation.
- Published
- 2021
38. EPHA2, a promising therapeutic target for hepatocellular carcinoma
- Author
-
Hao Wang and Wei Qiu
- Subjects
0301 basic medicine ,Cancer Research ,biology ,business.industry ,Erythropoietin-producing hepatocellular (Eph) receptor ,medicine.disease_cause ,medicine.disease ,EPH receptor A2 ,digestive system diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Tumor progression ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,STAT protein ,medicine ,biology.protein ,Cancer research ,Author’s Views ,Molecular Medicine ,Carcinogenesis ,STAT3 ,business ,Protein kinase B - Abstract
Identifying critical drivers of oncogenesis and tumor progression is essential for developing effective hepatocellular carcinoma (HCC) therapeutics. Our recent findings has demonstrated that targeting Ephrin Receptor A2 (EPHA2) suppresses HCC initiation and progression by dual inhibition of the Protein Kinase B (AKT) and Signal Transducer and Activator of Transcription 3 (STAT3) signaling.
- Published
- 2021
39. New link between the RNA polymerase II-CTD and replication stress
- Author
-
Lise E. Sandquist, Randi G. Syljuåsen, Lilli T. E. Bay, and Helga B. Landsverk
- Subjects
transcription-replication conflicts ,Cancer Research ,Protein subunit ,carboxy-terminal domain (CTD) ,RNA polymerase II ,Dephosphorylation ,Serine ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,Author’s Views ,030304 developmental biology ,0303 health sciences ,Replication stress ,biology ,Replication (computing) ,Cell biology ,PP1 nuclear targeting subunit (PNUTS) ,WD repeat-containing protein 82 (WDR82) ,biology.protein ,Molecular Medicine ,CTD ,PP1 phosphatase ,030217 neurology & neurosurgery ,Article Commentary - Abstract
Conflicts between transcription and replication are a major source of replication stress. Our recent findings show that proper dephosphorylation of Serine 5 in the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1 is needed to prevent such conflicts in human cells.
- Published
- 2021
40. The role of OFD1 in selective autophagy
- Author
-
Manuela Morleo, Brunella Franco, Franco, B, Morleo, M, Franco, B., and Morleo, M.
- Subjects
selective autophagy ,0303 health sciences ,Cancer Research ,Renal cystic disease ,Chemistry ,Mechanism (biology) ,Autophagy ,Mutant ,Cell biology ,autophagy receptor ,Selective autophagy ,03 medical and health sciences ,0302 clinical medicine ,Selective degradation ,Renal cysts ,renal cystic disease ,Oral-Facial-Digital type I syndrome ,Author’s Views ,Molecular Medicine ,OFD1 ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Autophagy is a cellular self-degradative pathway. Our study unveiled a novel mechanism mediated by OFD1, the protein mutated in Oral-Facial-Digital type I syndrome, based on selective degradation of autophagic proteins, which enables cells to calibrate their self-degradation. We demonstrated that unrestrained autophagy contributes to renal cysts observed in Ofd1 mutants.
- Published
- 2021
41. Targeting one-carbon metabolism requires mTOR inhibition: a new therapeutic approach in osteosarcoma
- Author
-
Brian A. Van Tine and Richa Rathore
- Subjects
0301 basic medicine ,Cancer Research ,mTORC1 ,methotrexate ,Serine ,serine ,03 medical and health sciences ,chemistry.chemical_compound ,perhexiline ,0302 clinical medicine ,Biosynthesis ,osteosarcoma ,medicine ,Author’s Views ,Phosphoglycerate dehydrogenase ,PHGDH ,PI3K/AKT/mTOR pathway ,Chemistry ,Cancer ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Perhexiline ,Cancer research ,Molecular Medicine ,Osteosarcoma ,medicine.drug ,Article Commentary - Abstract
The rate-limiting enzyme of serine biosynthesis, 3-phosphoglycerate dehydrogenase (PHGDH), contributes to rapid growth and proliferation when it is overexpressed in cancer. We recently described the metabolic adaptations that occur upon PHGDH inhibition in osteosarcoma. PHGDH inhibition causes metabolite accumulation that activates the mechanistic target of rapamycin (mTOR) signaling, sensitizing osteosarcoma to non-rapalog mTOR inhibition.
- Published
- 2021
42. Roles of SDE2 and TIMELESS at active and stalled DNA replication forks
- Author
-
Hyungjin Kim, Natalie Lo, and Julie Rageul
- Subjects
0301 basic medicine ,Genome instability ,Cancer Research ,Timeless ,DNA replication ,Regulator ,Biology ,Brca1 brca2 ,Replication (computing) ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Author’s Views ,Molecular Medicine ,Replisome - Abstract
The fork protection complex (FPC), comprising the TIMELESS (TIM)-TIPIN heterodimer, acts as a scaffold of the replisome to support seamless DNA replication. We recently showed that SDE2, a PCNA-associated DNA replication stress regulator, maintains the integrity of the FPC, and together with TIM, protects stalled replication forks from nucleolytic degradation.
- Published
- 2021
43. P53 orchestrates a complex symphony of cellular processes during oncosuppression
- Author
-
Laura D. Attardi and Liz J. Valente
- Subjects
0301 basic medicine ,Cancer Research ,Cellular functions ,Context (language use) ,P53 Tumor Suppressor ,Biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Author’s Views ,Molecular Medicine ,Gene ,Neuroscience ,030217 neurology & neurosurgery ,Protein p53 - Abstract
We recently showed that the p53 tumor suppressor simultaneously governs numerous cellular processes in one model of transformation suppression. These findings suggest that p53-mediated tumor suppression relies on coordinated modulation of diverse cellular functions in a particular context, helping to explain why loss of the TP53 (tumor protein p53) gene is so prevalent in human cancers.
- Published
- 2021
44. The pan-cancer lncRNA MILIP links c-Myc to p53 repression
- Author
-
Rick F. Thorne, Xiao Hong Zhao, Xudong Zhang, Yu Chen Feng, Liu Teng, and Lei Jin
- Subjects
0301 basic medicine ,p53 ,Cancer Research ,Pan cancer ,MILIP ,SUMO protein ,pan-cancer ,Biology ,Long non-coding RNA ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,c-Myc ,lncRNA ,030220 oncology & carcinogenesis ,Author’s Views ,Molecular Medicine ,Psychological repression ,Transcription factor ,Protein p53 ,Cell survival ,Article Commentary - Abstract
We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver. Our studies show that MILIP facilitates tumor protein p53 (TP53, best known as p53) turnover by reducing its SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2), thus promoting cell survival, proliferation, and tumorigenicity. MILIP may thus represent an anti-cancer target for counteracting the c-Myc axis.
- Published
- 2021
45. The senescence-associated secretory phenotype as a driver of tumor growth: does G3BP1 hold the key?
- Author
-
Sergio Di Marco, Imed-Eddine Gallouzi, and Amr Omer
- Subjects
0301 basic medicine ,Senescence ,G3BP1 ,Cancer Research ,Senescence-Associated Secretory Phenotype ,SASPs ,Mechanism (biology) ,Cellular senescence ,Cancer ,Context (language use) ,Biology ,medicine.disease ,Phenotype ,cancer progression ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine ,Author’s Views ,Molecular Medicine ,Tumor growth ,030217 neurology & neurosurgery ,Article Commentary - Abstract
Cellular senescence is a double-edged sword that, depending on the context, acts as either a potent tumor protective mechanism or an age-related driver of diseases such as cancer. Our recent findings show that the rasGAP SH3-binding protein 1 (G3BP1) activates the senescent-associated secretory phenotype (SASP) that, in turn, mediates cancer growth/progression.
- Published
- 2021
46. Ca
- Author
-
Eduardo, Silva-Pavez, Ulises, Ahumada-Castro, Alenka, Lovy, and Julio Cesar, Cárdenas
- Subjects
Author’s Views - Abstract
The inositol 1,4,5-triphosphate receptor (InsP3R)-mediated calcium (Ca(2+)) transfer to mitochondria is important to maintain mitochondrial respiration and bioenergetics in normal and cancer cells, even though cancer cells have defective oxidative phosphorylation (OXPHOS). Here, we discuss how tumor mitochondria could become a feasible therapeutic target to treat tumors that depend on reductive carboxylation.
- Published
- 2021
47. Topoisomerase I prevents transcription-replication conflicts at transcription termination sites
- Author
-
Yaqun Liu, Yea-Lih Lin, Philippe Pasero, Chun-Long Chen, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Cancer Research ,[SDV]Life Sciences [q-bio] ,topoisomerase I ,chromosome breaks ,03 medical and health sciences ,Chromosome Breaks ,chemistry.chemical_compound ,0302 clinical medicine ,Transcription (biology) ,Replication fork stalling ,Author’s Views ,Gene ,030304 developmental biology ,0303 health sciences ,biology ,Topoisomerase ,Transcription-replication conflict ,RNA ,R-loops ,Cell biology ,chemistry ,biology.protein ,Molecular Medicine ,Human genome ,030217 neurology & neurosurgery ,DNA ,Article Commentary - Abstract
International audience; R-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops, we mapped RNA:DNA hybrids, markers of replication fork stalling and DNA double-strand breaks along the human genome. This analysis indicates that transient replication fork pausing occurs at the transcription termination sites of highly expressed genes enriched in R-loops and prevents head-on conflicts with transcription, in a topoisomerase I-dependent manner.
- Published
- 2021
48. Bad to the bone: B cell acute lymphoblastic leukemia cells mediate bone destruction
- Author
-
Jayne S. Danska and Rajakumar Sujeetha
- Subjects
0301 basic medicine ,Cancer Research ,biology ,Activator (genetics) ,Effector ,business.industry ,RANKL ,B-ALL ,B-cell acute lymphoblastic leukemia ,Ligand (biochemistry) ,bone destruction ,03 medical and health sciences ,Patient diagnosis ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Author’s Views ,Molecular Medicine ,Medicine ,Receptor ,business ,Article Commentary - Abstract
Skeletal morbidities continue to cause acute and long-term burdens for B-ALL patients underscoring the need to identify the mechanisms underlying these processes and to develop effective therapies. Our recent findings demonstrated that B-ALL cells isolated at patient diagnosis can cause bone destruction and have identified the receptor activator of nuclear factor κ-B (RANK-RANKL) ligand axis as a critical effector of these effects.
- Published
- 2021
49. BOK-MCL1 transmembrane interactions: a challenging target for cancer therapy
- Author
-
Mar Orzáez and Mónica Sancho
- Subjects
0301 basic medicine ,Cancer Research ,Programmed cell death ,Myeloid ,Cell ,BCL-2 ,Apoptosis ,Biology ,03 medical and health sciences ,BOK ,0302 clinical medicine ,medicine ,Author’s Views ,MCL1 ,transmembrane domain ,medicine.disease ,Transmembrane protein ,Transmembrane domain ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Molecular Medicine ,030217 neurology & neurosurgery ,Article Commentary - Abstract
Myeloid cell leukemia 1 (MCL1) gene amplification occurs in a wide range of human cancers and protein overexpression associates with malignant cell growth and evasion of apoptosis. We recently reported that disrupting the interaction between the transmembrane domains of MCL1 and BCL-2 related ovarian killer (BOK) induces cell death, thereby suggesting a new target site for anti-tumorigenic strategies.
- Published
- 2021
50. Targeting ganglioneuromas with mTOR inhibitors
- Author
-
Hui Shi, Ting Tao, Adam D. Durbin, and A. Thomas Look
- Subjects
0301 basic medicine ,Cancer Research ,mTOR inhibitor ,Serine ,03 medical and health sciences ,0302 clinical medicine ,Author’s Views ,Medicine ,Ganglioneuroma ,Threonine ,Zebrafish ,Protein kinase B ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,biology ,business.industry ,Kinase ,AKT ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Molecular Medicine ,business ,zebrafish model ,Article Commentary - Abstract
We recently identified activated protein kinase B (PKB/AKT) as a tumorigenic driver in childhood ganglioneuroma. Inhibition of the mechanistic target of rapamycin (mTOR), a serine/threonine kinase downstream of AKT, effectively reduced the tumor burden in zebrafish with ganglioneuroma. We propose a clinical trial of mTOR inhibitors as a means to shrink large ganglioneuromas prior to surgical resection.
- Published
- 2021
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