Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

Triple-negative breast cancer comprises approximately 15–20% of all breast cancers diagnosed and is nearly twice as common in black women than white women in the United States. We evaluated the effects of two epigenetic-modifying compounds on markers of growth potential in several triple-negative breast cancer cell lines. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor currently used in the treatment of cutaneous T cell lymphoma, was administered to triple-negative breast cancer cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. The compounds affected the expression of oncogenic miR-221/222 and tumor suppressors, p27 and PTEN, in addition to estrogen receptor alpha (ERα). E-cadherin expression was increased while N-cadherin was decreased, indicating a more epithelial phenotype. In addition, the activity of DNMTs was diminished with the treatments, and there was a significant enrichment of AcH3 within the promoter of p27 and PTEN, suggesting a role of epigenetic mechanisms for the aforementioned changes. These results translated to reduced migration of the triple-negative breast cancer cells with the treatments. Together, these findings support the role of SAHA and EGCG in limiting growth and proliferation of breast cancer cells.

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BSCI-15. Osteopontin plays a crucial role in invasiveness of triple negative breast cancer cells in the context of human microglia

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab071.014 ◽

2021 ◽

Vol 3 (Supplement_3) ◽

pp. iii4-iii4

Author(s):

Kamil Wojnicki ◽

Agata Kochalska ◽

Katarzyna Poleszak ◽

Adria-Jaume Roura ◽

Ewa Matyja ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Metastatic Breast ◽

Breast Cancer Cell Lines ◽

Breast Cancers ◽

Human Microglia

Abstract The triple-negative breast cancer (TNBC) is the most malignant among breast cancers and has the high risk of developing metastasis into the brain. Metastases of breast cancers are increasing and pose a clinical challenge as the current treatments are not effective due to the unique brain microenvironment for metastatic breast cancer cells. While the contribution of brain macrophages to the formation of the metastatic niche is established, factors responsible for the crosstalk between cells remain elusive. SPP1 encoding a secreted phosphoprotein 1 (ostepontin) is highly overexpressed in malignant breast cancers. We evaluated the role of SPP1 in invasion and metastasis of human breast cancer cells. We found the increased invasion of triple-negative MDA-MB-231 (MDA-231) cells in the presence of human microglial HMSV40 cells. Using Western blot analysis demonstrated the elevated levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) in MDA-231 cells in co-cultures. Moreover, blocking SPP1 and integrin interactions with the synthetic RGD peptide, efficiently diminished both basic and microglia-induced invasion of MDA-231. To assess the role of SPP1 in cell invasion, we established the MDA-231 cells with knocked-down SPP1 expression using shRNA (shSPP1). Interestingly, the shSPP1 cells were unresponsive towards HMSV40 microglia. We have previously found that an antibiotic minocycline reduces SPP1 expression in glioma cells. We performed cell toxicity studies on 4 breast cancer cell lines and various non-malignant cells. All tested malignant cancer cells were more sensitize to minocycline than non-cancerous cells and breast cancer cells derived from TNBC were the most susceptible. Altogether, we demonstrate that microglia support invasion of breast cancer cells via SPP1/osteopontin triggering the integrin signalling, and minocycline by downregulating SPP1 expression may reduce both basic and microglia-induced cancer invasion. Therefore, we purpose that minocycline could be a new therapeutics targeting metastatic brain cancers.

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Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000443052 ◽

2016 ◽

Vol 38 (3) ◽

pp. 1003-1014 ◽

Cited By ~ 24

Author(s):

Aiyu Zhu ◽

Yan Li ◽

Wei Song ◽

Yumei Xu ◽

Fang Yang ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Cyclin D1 ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

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Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway

Toxicology Letters ◽

10.1016/j.toxlet.2013.05.006 ◽

2013 ◽

Vol 220 (3) ◽

pp. 219-228 ◽

Cited By ~ 54

Author(s):

Hongzhong Li ◽

Bing Yang ◽

Jing Huang ◽

Tingxiu Xiang ◽

Xuedong Yin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Growth Potential

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The Potential Prognostic Role of Oligosaccharide-Binding Fold-Containing Protein 2A (OBFC2A) in Triple-Negative Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.751430 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qianxue Wu ◽

Xin Tang ◽

Wenming Zhu ◽

Qing Li ◽

Xiang Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Candidate Genes ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

G1 Phase ◽

And Migration

BackgroundPatients with triple-negative breast cancer (TNBC) have poor overall survival. The present study aimed to investigate the potential prognostics of TNBC by analyzing breast cancer proteomic and transcriptomic datasets.MethodsCandidate proteins selected from CPTAC (the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium) were validated using datasets from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Kaplan-Meier analysis and ROC (receiver operating characteristic) curve analysis were performed to explore the prognosis of candidate genes. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed on the suspected candidate genes. Single-cell RNA-seq (scRNA-seq) data from GSE118389 were used to analyze the cell clusters in which OBFC2A (Oligosaccharide-Binding Fold-Containing Protein 2A) was mainly distributed. TIMER (Tumor Immune Estimation Resource) was used to verify the correlation between OBFC2A expression and immune infiltration. Clone formation assays and wound healing assays were used to detect the role of OBFC2A expression on the proliferation, invasion, and migration of breast cancer cells. Flow cytometry was used to analyze the effects of silencing OBFC2A on breast cancer cell cycle and apoptosis.ResultsSix candidate proteins were found to be differentially expressed in non-TNBC and TNBC groups from CPTAC. However, only OBFC2A was identified as an independently poor prognostic gene marker in METABRIC (HR=3.658, 1.881-7.114). And OBFC2A was associated with immune functions in breast cancer. Biological functional experiments showed that OBFC2A might promote the proliferation and migration of breast cancer cells. The inhibition of OBFC2A expression blocked the cell cycle in G1 phase and inhibited the transformation from G1 phase to S phase. Finally, downregulation of OBFC2A also increased the total apoptosis rate of cells.ConclusionOn this basis, OBFC2A may be a potential prognostic biomarker for TNBC.

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MiR-133 Targets YES1 and Inhibits the Growth of Triple-Negative Breast Cancer Cells

Technology in Cancer Research & Treatment ◽

10.1177/1533033820927011 ◽

2020 ◽

Vol 19 ◽

pp. 153303382092701

Author(s):

Guochen Zhang ◽

Junlan Wang ◽

Ruilin Zheng ◽

Beibei Song ◽

Li Huang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Colony Formation ◽

Breast Cancer Cells ◽

Triple Negative ◽

Mechanism Study ◽

Inhibitory Effects ◽

Cancer Tissues

Triple-negative breast cancer shows worse outcome compared with other subtypes of breast cancer. The discovery of dysregulated microRNAs and their roles in the progression of triple-negative breast cancer provide novel strategies for the treatment of patients with triple-negative breast cancer. In this study, we identified the significant reduction of miR-133 in triple-negative breast cancer tissues and cell lines. Ectopic overexpression of miR-133 suppressed the proliferation, colony formation, and upregulated the apoptosis of triple-negative breast cancer cells. Mechanism study revealed that the YES Proto-Oncogene 1 was a target of miR-133. miR-133 bound the 3′-untranslated region of YES Proto-Oncogene 1 and decreased the level of YES Proto-Oncogene 1 in triple-negative breast cancer cells. Consistent with miR-133 downregulation, YES1 was significantly increased in triple-negative breast cancer, which was inversely correlated with the level of miR-133. Restoration of YES Proto-Oncogene 1 attenuated the inhibitory effects of miR-133 on the proliferation and colony formation of triple-negative breast cancer cells. Consistent with the decreased expression of YES Proto-Oncogene 1, overexpression of miR-133 suppressed the phosphorylation of YAP1 in triple-negative breast cancer cells. Our results provided novel evidence for the role of miR-133/YES1 axis in the development of triple-negative breast cancer, which indicated miR-133 might be a potential therapeutic strategy for triple-negative breast cancer.

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Abstract 1330: Role of epigenetic remodeling in sensitizing triple-negative breast cancer cells to treatment through enhanced chemotherapy-induced autophagy

10.1158/1538-7445.am2018-1330 ◽

2018 ◽

Author(s):

Liliya Tyutyunyk ◽

Joseph Landry ◽

David Gewirtz ◽

Nga Dao

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Epigenetic Remodeling

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Novel role of PELP1 in regulating chemotherapy response in mutant p53-expressing triple negative breast cancer cells

Breast Cancer Research and Treatment ◽

10.1007/s10549-015-3339-x ◽

2015 ◽

Vol 150 (3) ◽

pp. 487-499 ◽

Cited By ~ 12

Author(s):

Samaya R. Krishnan ◽

Binoj C. Nair ◽

Gangadhara R. Sareddy ◽

Sudipa Saha Roy ◽

Mohan Natarajan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Chemotherapy Response ◽

Mutant P53

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SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation

10.21203/rs.3.rs-105332/v1 ◽

2020 ◽

Author(s):

Xiaofeng Dai ◽

Lihui Yu ◽

Xiao Chen ◽

Jianying Zhang

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Expression Patterns ◽

Chemotherapy Response ◽

Gene And Protein Expression

Abstract Background SNRPD1 is a spliceosome-associated protein and has previously been implicated with important roles in cancer development. Methods Through analyzing the differential expression patterns and clinical association of splicing associated genes among tumor and tumor adjacent samples across different tumors and among different breast cancer subtypes, we identify the tumor promotive role of SNRPD1 using multiple publicly available datasets. Through pathway, gene ontology enrichment analysis and network construction, we linked the onco-therapeutic role of SNRPD1 with cell cycle. Via a series of experimental studies including knockdown assay, qPCR, western blotting, cell cycle, drug response assay, we confirmed the higher expression of SNPRD1 at both gene and protein expression levels in triple negative breast cancer cells, as well as its roles in promoting cell cycle and chemotherapy response. Results Our study revealed that SNRPD1 over-expression was significantly associated with genes involved in cell cycle, cell mitosis and chromatin replication, and silencing SNRPD1 in breast cancer cells could lead to halted tumor cell growth and cell cycle arrest at the G0/G1 stage. We also found that triple negative breast cancer cells with reduced SNRPD1 expression gained reduced sensitivity to doxorubicin whereas luminal cancer cells did not. Conclusions Our results suggested the prognostic value of SNRPD1 on breast cancer survival, its potential as the therapeutic target halting cell cycle progression for breast cancer control, and warranted special attention on the combined use of doxorubicin and drugs targeting SNRPD1.

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