ERα signaling through slug regulates E-cadherin and EMT

Ye, Y; Xiao, Yi; Wang, W; Yearsley, Kurtis; Gao, Jian; Shetuni, Brandon S.; Barsky, Sanford H.

doi:10.1038/onc.2009.433

Cited by 166 publications

(149 citation statements)

References 48 publications

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“…In recent years, epithelial-mesenchymal transition (EMT) has been recognized as a key step during the progression of primary tumors into metastases as well as its original role during embryogenesis (31,32). ERα signaling through Slug regulates E-cadherin and EMT (33). In our study, consistent decrease of both the epithelial marker and ERα suggested EMT features, which could explain the acquisitions of tumorigenesis and invasive capacity.…”

Section: Discussionmentioning

confidence: 67%

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

et al. 2012

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Abstract. Cancer/testis antigen (CTA) SSX2, which is silent in most normal adult tissues and expressed in various malignant tumors, has been identified for decades. Expression of SSX in tumors has been associated with advanced stages and worse patient prognosis. However, little is known about its role in breast cancer. The SSX2 expression plasmid constructed was stably transfected into the breast cancer cell line MCF-7. The influence of SSX2 on MCF-7 cells was assessed using MTT assay, flow cytometry, transwell invasion assay and in vivo tumorigenicity assay. A comparative proteomic approach was performed to identify and clarify the underlying molecular mechanisms. SSX2 expression was more pronounced in ERα-negative breast cancer cells compared with the positive ones. Overexpression of SSX2 induced cell growth and prompted cell invasion. Both ERα and E-cadherin expression were suppressed in the SSX2 overexpressing MCF-7 cells. Eleven known proteins were identified with significant differential expression. Among these, five were decreased, while other six were increased in the SSX2 overexpressing MCF-7 cells. These results suggested SSX2 may enhance invasiveness in MCF-7 cells both in vivo and in vitro. The regulation of ERα signaling by target proteins of SSX2 may explain the metastatic potential of breast cancer cells.

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Section: Discussionmentioning

confidence: 67%

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

et al. 2012

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“…CK expression in triple-negative tumor CTCs requires additional study and a larger sample population. Expression of PR indicates a functional ERα (one of the two isoforms of ER) and ERα pathway (23), which increases E-cadherin expression by downregulating transcriptional repressors (24,25). Patients with Her2-positive tumors lack ER and PR expression, which decreases the level of E-cadherin, and enhances the possibility of EMT and tumor cell invasion.…”

Section: Discussionmentioning

confidence: 99%

Characterization of circulating tumor cells in newly diagnosed breast cancer

Jia

et al. 2017

Oncol Lett

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Abstract. Identification of circulating tumor cells (CTCs)by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)-and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression.

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“…Because previous studies have shown that ERα and FOXA1 are involved in E-cadherin expression, 20,21) we investigated the genes important for E-cadherin expression in breast cancer cells by stable expression of each gene in MDA-MB-231 cells. Although E-cadherin expression was profoundly induced at the mRNA and protein levels by stable expression of FOXA1, ERα expression did not affect E-cadherin expression (Figs.…”

Section: Foxa1 Induces E-cadherin Expression Independently Of Erαmentioning

confidence: 99%

FOXA1 Induces E-Cadherin Expression at the Protein Level <i>via</i> Suppression of Slug in Epithelial Breast Cancer Cells

Anzai

Hirata

Shibazaki

et al. 2017

Biological & Pharmaceutical Bulletin

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Epithelial-to-mesenchymal transition (EMT) is an important process during embryonic development and tumor progression by which adherent epithelial cells acquire mesenchymal properties. Forkhead box protein A1 (FOXA1) is a transcriptional regulator preferentially expressed in epithelial breast cancer cells, and its expression is lost in mesenchymal breast cancer cells. However, the implication of this biased expression of FOXA1 in breast cancer is not fully understood. In this study, we analyzed the involvement of FOXA1 in EMT progression in breast cancer, and found that stable expression of FOXA1 in the mesenchymal breast cancer MDA-MB-231 cells strongly induced the epithelial marker E-cadherin at the mRNA and protein levels. Furthermore, stable expression of FOXA1 was found to reduce the mRNA and protein expression of Slug, a repressor of E-cadherin expression. FOXA1 knockdown in the epithelial breast cancer MCF7 cells reduced E-cadherin protein expression without decreasing its mRNA expression. In addition, FOXA1 knockdown in MCF7 cells up-regulated Slug mRNA and protein expression. Notably, similar to FOXA1 knockdown, stable expression of Slug in MCF7 cells reduced E-cadherin protein expression without decreasing its mRNA expression. Taken together, these results suggest that although FOXA1 can induce E-cadherin mRNA expression, it preferentially promotes E-cadherin expression at the protein level by suppressing Slug expression in epithelial breast cancer, and that the balance of this FOXA1-Slug axis regulates EMT progression.Key words epithelial-mesenchymal transition; E-cadherin; forkhead box protein A1; Slug; estrogen receptor Epithelial-to-mesenchymal transition (EMT) is a process that converts adherent epithelial cells to motile mesenchymal cells during embryonic development. 1) EMT is also involved in tumor progression through inducing metastasis and chemoresistance in tumor cells.2-4) Therefore, a better understanding of the molecular mechanisms underlying EMT in tumor cells is beneficial for development of novel antitumor agents.E-Cadherin is a crucial protein that mediates cell-cell adhesion in epithelial cells.1) E-Cadherin expression is dramatically reduced during EMT, which causes loss of cell-cell adhesion and gain of cell motility. Reduction in E-cadherin expression is mainly caused by the transcriptional repressors of E-cadherin gene (CDH1).2,5) A major transcriptional repressor of CDH1 is the zinc finger factor Slug. Slug binds to the E-box sequences present in the enhancer region of CDH1 and represses its expression. 6)Forkhead box A1 (FOXA1) is a member of the forkhead box family of transcription factors. FOXA1 contains the forkhead DNA-binding domain and the N-and C-terminal transactivation domains.7) FOXA1 regulates expression of many genes involved in the development of various tissues, including mammary gland, liver, midbrain, and lung. 8) FOXA1 is also known to function as a chromatin remodeling factor that opens closed chromatin and facilitates the recruitment of other transcription fa...

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ERα signaling through slug regulates E-cadherin and EMT

Cited by 166 publications

References 48 publications

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

Characterization of circulating tumor cells in newly diagnosed breast cancer

FOXA1 Induces E-Cadherin Expression at the Protein Level <i>via</i> Suppression of Slug in Epithelial Breast Cancer Cells

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