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Objective: Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers, because it sustains cancer cell survival, proliferation, and metastasis. The acyl-CoA synthetase long-chain (ACSL) family is known to activate long-chain fatty acids, yet the specific role of ACSL3 in breast cancer has not been determined., Methods: We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples. Gain-of-function and loss-of-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo ., Results: ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues, and this phenotype correlated with improved survival outcomes. Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation, migration, and epithelial-mesenchymal transition. Mechanistically, ACSL3 was found to inhibit β-oxidation and the formation of associated byproducts, thereby suppressing malignant behavior in breast cancer. Importantly, ACSL3 was found to interact with YES proto-oncogene 1, a member of the Src family of tyrosine kinases, and to suppress its activation through phosphorylation at Tyr419. The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation, and the expression of its downstream genes in breast cancer cell nuclei., Conclusions: ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming, and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways. These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer., Competing Interests: No potential conflicts of interest are disclosed., (Copyright: © 2024, The Authors.)

Purpose of Review: The purpose of this review was to describe the characteristics of breast cancer cells prone to developing bone metastasis and determine how they are regulated by the bone microenvironment., Recent Findings: The bone is a site of frequent breast cancer metastasis. Bone metastasis accounts for 70% of advanced breast cancer cases and remains incurable. It can lead to skeletal-related events, such as bone fracture and pain, and seriously affect the quality of life of patients. Breast cancer cells escape from the primary lesion and spread to the bone marrow in the early stages. They can then enter the dormant state and restore tumourigenicity after several years to develop overt metastasis. In the last few years, an increasing number of studies have reported on the factors promoting bone metastasis of breast cancer cells, both at the primary and metastatic sites. Identifying factors associated with bone metastasis aids in the early recognition of bone metastasis tendency. How to target these factors and minimize the side effects on the bone remains to be further explored., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC)., Methods: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments., Results: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy., Conclusions: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer., Methods: ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan-Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB)., Results: ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score., Conclusions: Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration., (© 2023. The Author(s).)

Background: Triple-positive breast cancer (TPBC) is a tumor that simultaneously expresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Luminal A-like TPBC is a special subtype with a favorable prognosis but benefits less from HER2-targeted therapy. However, little is known about how to identify luminal A-like TPBCs. Therefore, our study aims to explore a clinically feasible method to identify luminal A-like TPBCs using immunohistochemical (IHC) markers., Methods: Our cohort enrolled consecutive 190 patients with early-stage TPBCs diagnosed, treated and followed up in our hospital between 2013 and 2019. Patients whose IHC staining displayed ≥ 50% in both ER and PR scores and B-cell lymphoma 2 (BCL2) positivity were classified as cohort A (n = 64), and the rest were enrolled in cohort B (n = 126). Kaplan-Meier plotter and log-rank test were used to compare the survival difference between cohort A and cohort B and the efficacy of trastuzumab therapy in the two cohorts., Results: The disease-free survival (DFS) of patients in cohort A was significantly better than in cohort B (p = 0.031). In cohort A, there was no statistically significant difference in DFS between patients treated with trastuzumab and those without trastuzumab (p = 0.663). While in cohort B, patients treated with trastuzumab had significantly better DFS than those without trastuzumab (p = 0.032). Multivariate survival analysis showed that cohort A was associated with better DFS(95%CI 1.046-11.776, p = 0.042)., Conclusion: TPBCs consist of heterogeneous subtypes. Detecting the expression of ER, PR and BCL2 via IHC can help identify luminal A-like TPBCs. This study will enable individualized treatment of TPBCs., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Obesity is a well-known modifiable risk factor for breast cancer and is considered a poor prognostic factor in pre- and post-menopausal women. While the systemic effects of obesity have been extensively studied, less is known about the mechanisms underlying obesity-associated cancer risk and the local consequences of obesity. Thus, obesity-induced inflammation has become the focus of research interest. Biologically, the development of cancer involves a complex interaction with numerous components. As the tumor immune microenvironment changes due to obesity-triggered inflammation, an increase in infiltration occurs for proinflammatory cytokines and adipokines, as well as adipocytes, immune cells, and tumor cells in the expanded adipose tissue. Complicated cellular-molecular crosstalk networks change critical pathways, mediate metabolic and immune function reprogramming, and have a significant role in tumor metastasis, proliferation, resistance, angiogenesis, and tumorigenesis. This review summarizes recent research findings on how inflammatory mediators in the in situ tumor microenvironment regulate the occurrence and development of breast cancer in the context of obesity. We analyzed the heterogeneity and potential mechanisms of the breast cancer immune microenvironment from the perspective of inflammation to provide a reference for the clinical transformation of precision targeted cancer therapy., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2023 Cancer Biology & Medicine.)

Metastasis of breast cancer represents the major reason for its poor prognosis, leading to high mortality. In breast cancer, a tumor suppressor gene TP53 is commonly mutated. TP53 mutation leads to an altered expression of various genes, an event that is associated with aggressive tumor and is a strong independent marker for survival. In this study, we identified a novel p53 target gene, immunoglobulin superfamily 9 (IGSF9). IGSF9 is generally down-regulated in breast cancer tissues. Loss of IGSF9 is associated with frequent metastasis and poor prognosis of breast cancer patients. Wild-type p53, but not R175H mutant, trans-activates the transcription of IGSF9 via binding to its promoter (-137 to -131 bp), inhibits epithelial-mesenchymal transition (EMT), consequently the inhibition of breast cancer cells migration and invasion. IGSF9 interacts with focal adhesion kinase (FAK) and inhibits FAK/AKT signaling activity. PND1186, FAK inhibitor, inhibits breast cancer metastasis induced by IGSF9 knockdown in vitro and in vivo. Taken together, IGSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. IGSF9 could serve as a prognostic marker and potential therapeutic target for breast cancer., (© 2022. The Author(s).)

Purpose: Paclitaxel, belongs to tubulin-binding agents (TBAs), shows a great efficacy against breast cancer via stabilizing microtubules. Drug resistance limits its clinical application. Here we aimed to explore a role of Polarity protein Par3 in improving paclitaxel effectiveness., Methods: Breast cancer specimens from 45 patients were collected to study the relationship between Par3 expression and paclitaxel efficacy. The Kaplan-Meier method was used for survival analysis. Cell viability was measured in breast cancer cells (SK-BR-3 and T-47D) with Par3 over-expression or knockdown. The flow cytometry assays were performed to measure cell apoptosis and cell cycle. BrdU incorporation assay and Hoechst 33,258 staining were performed to measure cell proliferation and cell apoptosis, respectively. Immunofluorescence was used to detect microtubule structures., Results: Par3 expression was associated with good response of paclitaxel in breast cancer patients. Consistently, Par3 over-expression significantly sensitized breast cancer cells to paclitaxel by promoting cell apoptosis and reducing cell proliferation. In Par3 overexpressing cells upon paclitaxel treatment, we observed intensified cell cycle arrests at metaphase. Further exploration showed that Par3 over-expression stabilized microtubules of breast cancer cells in response to paclitaxel and resists to microtubules instability induced by nocodazole, a microtubule-depolymerizing agent., Conclusion: Par3 facilitates polymeric forms of tubulin and stabilizes microtubule structure, which aggravates paclitaxel-induced delay at the metaphase-anaphase transition, leading to proliferation inhibition and apoptosis of breast cancer cells. Par3 has a potential role in sensitizing breast cancer cells to paclitaxel, which may provide a more precise assessment of individual treatment and novel therapeutic targets., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Ki67 value and its variation before and after neoadjuvant chemotherapy are commonly tested in relation to breast cancer patient prognosis. This study aims to quantify the extent of changes in Ki67 proliferation pre- and post-neoadjuvant chemotherapy, confirm an optimal cut-off point, and evaluate its potential value for predicting survival outcomes in patients with different molecular subtypes of breast cancer. Methods: This retrospective real-world study recruited 828 patients at the Department of Breast Surgery of the First Affiliated Hospital of China Medical University and the Cancer Hospital of China Medical University from Jan 2014 to Nov 2020. Patient demographic features and disease pathology characteristics were recorded, and biomarkers were verified through immunohistochemistry. Various statistical methods were used to validate the relationships between different characteristics and survival outcomes irrespective of disease-free and overall survival. Results: Among 828 patients, statistically significant effects between pathological complete response and survival outcome were found in both HER2-enriched and triple-negative breast cancer ( p < 0.05) but not in Luminal breast cancer ( p > 0.05). Evident decrease of Ki67 was confirmed after neoadjuvant chemotherapy. To quantify the extent of Ki67 changes between pre- and post-NAC timepoints, we adopted a computational equation termed ΔKi67% for research. We found the optimal cut-off value to be " ΔKi67% = -63%" via the operating characteristic curve, defining ΔKi67% ≤ -63% as positive status and ΔKi67% > -63% as negative status. Patients with positive ΔKi67% status were 37.1% of the entire cohort. Additionally, 4.7, 39.9, 34.5 and 39.6% of patients with Luminal A, Luminal B, HER2-enriched and triple negative breast cancer were also validated with positive ΔKi67% status. The statistically significant differences between ΔKi67% status and prognostic outcomes were confirmed by univariate and multivariate analysis in Luminal B (univariate and multivariate analysis: p < 0.05) and triple negative breast cancer (univariate and multivariate analysis: p < 0.05). We proved ΔKi67% as a statistically significant independent prognostic factor irrespective of disease-free or overall survival among patients with Luminal B and triple-negative breast cancer. Conclusions: ΔKi67% can aid in predicting patient prognostic outcome, provide a measurement of NAC efficacy, and assist in further clinical decisions, especially for patients with Luminal B breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Fu, Xu, Qiu, Lv, Xu and Zhang.)

Oxidized low-density lipoprotein receptor 1 (OLR1), a key receptor for oxidized low-density lipoprotein (ox-LDL), plays a crucial role in cancer and inflammatory disease. However, the correlation between OLR1 expression and immune infiltration in breast cancer (BC) remain unclear. In this study, we comprehensively analyzed the expression level of OLR1 in BC tissues and explore the prognostic importance of OLR1 using quantitative real-time PCR, immunohistochemical analysis and different databases. The significantly enriched KEGG and GO pathways were used to identify the potential biological function of OLR1 via LinkedOmics analysis. Furthermore, we detected the correlation between OLR1 expression and a variety of immune infiltrating cells via Tumor Immune Estimation Resource database and GEPIA database. Our study revealed that OLR1 upregulation was observed in BC tissues and correlated with worse clinical outcomes and advanced clinicopathological factors. Meanwhile, OLR1 regulated various immunity-related pathways, especially the polarization of macrophages. Immunohistochemical analysis further confirmed the significant correlation between OLR1 expression and tumor infiltration of M2 macrophages as well as tumor-associated macrophages. OLR1 upregulation indicated poor prognosis in BC, possibly through inducing macrophage polarization and triggering immune evasion. Collectively, OLR1 may represent a potential therapeutic target for BC tailored therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hypoxia is a hallmark of the physical microenvironment of solid tumors. As a key factor that regulates tumor development and progression, hypoxia can reprogram the expression of multiple genes, whose biological function and molecular mechanism in cancer remain largely unclear. The mitochondrial ribosome protein family consists of nuclear-encoded mitochondrial proteins that are responsible for protein synthesis in the mitochondria. Methods: A high-throughput RNA sequencing assay was carried out to identify differentially expressed mRNAs between breast cancer tissues and adjacent normal tissues as well as breast tumors with metastasis and those without metastasis. Our clinical samples and TCGA database were analyzed to observe the clinical value of mitochondrial ribosome protein L52 (MRPL52) in human breast cancer. Potent hypoxia response elements in the promoter region of MRPL52 were identified and validated by chromatin immunoprecipitation and luciferase reporter assays. Functional experiments were performed using breast cancer cell lines with MRPL52 ectopic expression and knockdown cultured in a 20% or 1% O 2 environment. Results: MRPL52 expression was upregulated in human breast cancer and was significantly associated with aggressive clinicopathological characteristics and a higher metastatic risk of breast cancer patients. We found that the overexpression of MRPL52 in breast cancer is induced by hypoxia-inducible factor-1 in response to hypoxic exposure. The role of MRPL52 in suppressing apoptosis and promoting migration and invasion of hypoxic breast cancer cells was demonstrated by our experimental evidence. Mechanistically, MRPL52 promoted PTEN-induced putative kinase 1 /Parkin-dependent mitophagy to remove oxidatively damaged mitochondria and prevent uncontrolled reactive oxygen species (ROS) generation, thus repressing activation of the mitochondrial apoptotic cascade. Additionally, MRPL52 augmented epithelial-mesenchymal transition, migration and invasion of hypoxic breast cancer cells by activating the ROS-Notch1-Snail signaling pathway. Benefited from this bidirectional regulatory mechanism, MRPL52 is responsible for maintaining ROS levels in a window that can induce tumorigenic signal transduction without causing cytotoxicity in hypoxic breast cancer cells. Conclusions: This work elucidates the molecular mechanism by which MRPL52 mediates hypoxia-induced apoptotic resistance and metastatic initiation of breast cancer, and provides new insights into the interplay between cancer and the tumor microenvironment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe 2 O 4 @MnFe 2 O 4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.

Breast cancer (BC) is an aggressive malignant disease in women worldwide with a high tendency to metastasize. However, important biomarkers for BC metastasis remain largely undefined. In the present study, we identified that long non-coding RNA-CTD-2108O9.1 is downregulated in BC tissues and cells and acts as a metastatic inhibitor of BC. Mechanistic investigation determined that lncRNA-CTD-2108O9.1 represses metastasis by targeting leukemia inhibitory factor receptor (LIFR), which is designated as a metastasis suppressor in BC. Our study characterizes a significant tumor suppressor active in BC metastasis repression through the known metastasis inhibitor LIFR., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background/aims: This study aimed to explore the prognostic value of aldehyde dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with breast cancer., Methods: ALDH1 expression and the presence of VM were examined by immunohistochemistry and CD31/PAS double staining, respectively, using formalin-fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow-up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot survival curves. Prognostic values were assessed by multivariate analysis using the Cox regression model., Results: ALDH1 expression was strongly associated with VM (P = 0.005). ALDH1 expression was positively correlated with histological grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the status of the estrogen receptor and progesterone receptor and were statistically increased in triple-negative breast cancer. Patients with ALDH1 expression or VM displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1-negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM-double-positive patients. ALDH1-positive and VM-positive were independent survival risk factors for DFS and OS., Conclusion: ALDH1 expression and VM are correlated with the survival rate of patients with breast cancer. ALDH1 and VM, either alone or together, are prognostic factors in patients with breast cancer., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Transmembrane 4 L6 family member 1 (TM4SF1) belongs to the 4-transmembrane-domain family and functions as an oncogene in multiple human cancers. In this work, we aim to determine TM4SF1 expression and its prognostic impact on patients with invasive breast cancer.Overall, we enrolled 209 invasive breast cancer patients and immunohistochemically examined the expression of TM4SF1 in tumor specimens. The relationship between TM4SF1 expression and clinicopathological parameter and patient survival of breast cancer patients was analyzed.Among the 209 cases, 137 (65.6%) exhibited high expression of TM4SF1. High TM4SF1 expression was significantly associated with advanced histological grade and negative estrogen receptor and progesterone receptor status. Triple-negative breast cancer (TNBC) tumors were more likely to express high levels of TM4SF1 than non-TNBC cases. Patients with high tumoral expression of TM4SF1 had a significantly shorter disease-free survival (DFS; P = .00) and overall survival (OS; P = .01) than those with low expression of TM4SF1. When survival analysis was restricted to the 167 patients (79.9%) receiving adjuvant chemotherapy, TM4SF1 expression was also correlated with poorer DFS and OS (P = .00). In multiple Cox regression analysis TM4SF1 expression remained an independent prognostic indicator for OS and DFS.TM4SF1 is upregulated and serves as an independent poor prognostic indicator in invasive breast cancer., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Sleep patterns have been associated with the development of cancers, although the association between sleep duration and breast cancer remains controversial. The purpose of our study was to explore the relationship between sleep duration and breast cancer risk. The PubMed and Web of Science databases were searched, and restricted cubic splines were used to explore the dose-response relationship. Data from 415,865 participants were derived from 10 studies. A J-shaped nonlinear trend was found between sleep duration and breast cancer incidence ( P non-linear = 0.012); compared with the reference hours (6 h or 7 h), with increasing sleep hours, the risk of breast cancer increased ( P trend = 0.028). Moreover, a nonlinear relationship was found between sleep duration and estrogen receptor-positive breast cancer ( P non-linear = 0.013); the risk of estrogen receptor-positive breast cancer increased with increasing sleep hours compared to the reference hours ( P trend = 0.024). However, no nonlinear relationship was found between sleep duration and estrogen receptor-negative breast cancer; the risk of estrogen receptor-negative breast cancer was 1.035 for every additional sleep hour. Compared to women with the reference number of sleep hours, women with a longer sleep duration might have a significantly increased risk of breast cancer, especially estrogen receptor-positive breast cancer.

Cancer stem cells (CSCs) have been identified in a variety of cancers and emerged as a new target for cancer therapy. CSCs are resistant to many current cancer treatments, including chemotherapy and radiation therapy. Therefore, eradication of this cell population is a primary objective in cancer therapy. Here, we report gold nanorods (AuNRs) mediated photothermal treatment can selectively eliminate CSCs in MCF-7 breast cancer cells. It significantly reduced the aldehyde dehydrogenase positive (ALDH(+)) cells subpopulation and the mammosphere formation ability of treated cells. Also, the gene expression of stem cell markers was decreased. Cellular uptake assay revealed that polyelectrolyte conjugated AuNRs could be internalized by CSCs much more and faster than non cancer stem cells (NCSCs), which might be the main reason for the selective elimination of CSCs. We further loaded salinomycin (SA), a CSCs inhibitor with polyelectrolyte conjugated AuNRs to get a synergistic CSCs inhibition. Enhanced inhibition of CSCs was obtained by NIR light triggered drug release and hyperthermia. This CSCs-targeted thermo-chemotherapy platform provides a new combinatorial strategy for efficient inhibition of CSCs, which is promising to improve cancer treatment and may overcome the chemoresistance and recurrence of cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Crk-like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. However, the expression pattern of CRKL protein and its clinical significance in human breast cancers have not been well characterized. In this study, expression of CRKL was evaluated in 108 human invasive ductal carcinoma (IDC) tissues by immunohistochemistry. CRKL protein was upregulated in the cancer tissues compared with adjacent normal mammary glands. Overexpression of CRKL was found in 40 of 108 (37.03 %) breast cancer samples and correlated with advanced p-tumor-node-metastasis stage (p = 0.002), nodal metastasis (p = 0.0323), and tumor size (p = 0.0075). In addition, overexpression of CRKL in the MDA-MB-435 cell line promoted cell proliferation, and small interfering RNA knockdown of CRKL in the MDA-MB-453 cell line inhibited proliferation. Further analysis of cell cycle-related molecules showed that CRKL induced cyclin D1 and phosphorylated extracellular signal-regulated kinase expression. In conclusion, this study demonstrated that overexpression of CRKL correlated with progression and malignant proliferation of human breast cancers.

CARMA3 was recently reported to be overexpressed in several cancers and associated with malignant behavior of cancer cells. However, the expression pattern and biological roles of CARMA3 in breast cancer have not been reported. In the present study, we found that CARMA3 was overexpressed in 41.9 % of breast cancer specimens. Significant association was observed between CARMA3 overexpression and TNM stage (p = 0.0223), tumor size (p = 0.0227), and ErbB-2 status (p = 0.0049). Furthermore, knockdown of CARMA3 expression in MDA-MB-435 cells with high endogenous expression decreased cell proliferation and sensitized cell to paclitaxel-induced apoptosis, while overexpression of CARMA3 in MDA-MB-231 cell line promoted cell proliferation and inhibited apoptosis. Further analysis showed that CARMA3 depletion downregulated, and its overexpression upregulated cyclin D1, Bcl-2, and p-IκB levels. In conclusion, our study demonstrated that CARMA3 is overexpressed in breast cancers. CARMA3 facilitates proliferation and inhibits apoptosis through nuclear factor-kappaB signaling.

Aims: The LIM domain only proteins (LMOs) which consist of four members (LMO1-LMO4) are a family of nuclear transcription coregulators that are characterized by the exclusive presence of two tandem LIM domains and no other functional domains. They regulate gene transcription by functioning as "linker" or "scaffolding" proteins by virtue of their LIM domains and are involved in the formation of multiprotein complexes with several DNA-binding factors and transcriptional regulatory proteins. In the present study, we tried to find the physical interaction between p53 and LMO4, and the effect of LMO4 on p53-mediated proliferative inhibition of breast cancer cells., Main Methods: FCM analysis was developed to detect the apoptosis of breast cancer cells after adriamycin (ADR) treatment. RT-PCR and Western blot analysis were performed to detect the expression of LMO4 and p53-related genes and proteins. Immunoprecipitation assay was used to detect the interaction between LMO4 and p53. Colony formation assay was developed to detect the proliferation of breast cancer cells., Key Findings: We found that p53 was induced, but LMO4 was down-regulated in response to ADR. We also found that enforced expression of p53 inhibited the expression of LMO4, suggesting that LMO4 is a direct transcriptional target of p53. Furthermore, LMO4 can interact with p53 and inhibit p53-mediated inhibition of colony formation of breast cancer MDA-MB-453 cells., Significance: The present study showed that LMO4 is a direct target of p53 and inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Melanoma-associated antigens-A (MAGE-A) family is a group of well-characterized cancer/testis antigens (CTA), because they are strictly tumor specific and are shared by many kinds of tumors. However, the expression pattern of MAGE-A10 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our study is to investigate the expression pattern and prognostic significance of MAGE-A10 and MAGE-A11 in breast cancer patients., Methods: Formalin-fixed and paraffin-embedded tissues and the clinicopathological parameters from 75 primary breast cancer patients were collected. The expressions of MAGE-A10 and MAGE-A11 proteins were immunohistochemically detected, and the association of MAGE-A10 and MAGE-A11 expressions with the clinicopathological parameters and the survival of breast cancer patients were analyzed., Results: The expression rates of MAGE-A10 and MAGE-A11 in breast cancer specimens were 73.3 and 52.0%, respectively. MAGE-A11 expression was more frequent in estrogen-receptor (ER)-positive breast carcinomas compared with ER-negative breast carcinomas (P = 0.004). MAGE-A11 expression was positively associated with HER-2 expression (P = 0.003). Overall survival of patients with MAGE-A11-negative expression was significantly longer than those patients with positive MAGE-A11 expression (P = 0.030), but no difference of overall survival was found between patients with MAGE-A10-negative and -positive expression (P = 0.881)., Conclusions: MAGE-A10 and MAGE-A11 are tumor-specific antigens, and MAGE-A11 expression probably is a potential poor prognostic factor for breast cancer patients.