ArticleOncogenesis2017
The zinc-finger transcriptional factor Slug transcriptionally downregulates ERα by recruiting lysine-specific demethylase 1 in human breast cancer.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Prognostic and clinicopathological value of Slug protein expression in breast cancer: a systematic review and meta-analysis.World journal of surgical oncology · 2022Pooled it
- Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer.NPJ systems biology and applications · 2024Article
- Methylation ofMedComm · 2023Article
- Molecular mechanisms of TWIST1-regulated transcription in EMT and cancer metastasis.EMBO reports · 2023Article
- Article
- PD-L1 aptamer-functionalized degradable hafnium oxide nanoparticles for near infrared-II diagnostic imaging and radiosensitization.Frontiers in bioengineering and biotechnology · 2023Article
- Effects of Combined Pentadecanoic Acid and Tamoxifen Treatment on Tamoxifen Resistance in MCF-7/SC Breast Cancer Cells.International journal of molecular sciences · 2022Article
- The emerging role of ubiquitin-specific protease 20 in tumorigenesis and cancer therapeutics.Cell death & disease · 2022Review
- TGFα-EGFR pathway in breast carcinogenesis, association with WWOX expression and estrogen activation.Journal of applied genetics · 2022Article
- A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.Frontiers in pharmacology · 2022Review
- Mechanisms of carcinogenic activity triggered by lysine-specific demethylase 1A.Frontiers in pharmacology · 2022Review
- CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinomaPeerJ · 2022Article
- A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells.NAR cancer · 2021Article
- Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way.Frontiers in cell and developmental biology · 2021Review
- HES1 promotes breast cancer stem cells by elevating Slug in triple-negative breast cancer.International journal of biological sciences · 2021Article
- Upregulation of SOX11 enhances tamoxifen resistance and promotes epithelial-to-mesenchymal transition via slug in MCF-7 breast cancer cells.Journal of cellular physiology · 2020Article
- Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.Genes & development · 2020Article
- Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1.Hormones & cancer · 2020Review
- Notch Signaling Pathway and Endocrine Resistance in Breast Cancer.Frontiers in pharmacology · 2020Review
- Slug and E-Cadherin: Stealth Accomplices?Frontiers in molecular biosciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen receptor α (ERα) is related with epithelial-mesenchymal transition, invasion and metastasis, and serves as an important therapeutic predictor and prognostic factor in breast cancer patients. The triple negative breast cancer (TNBC) is characterized by loss of hormone receptors and human epidermal growth factor receptor 2 (Her2), and lacks effective targeted therapy with poor prognosis. Unfortunately, the molecular mechanisms of ERα deficiency, which becomes hormone independent and results in resistance to endocrine therapy, remain to be elucidated in breast cancer. In this study, we observed an inverse correlation between Slug, a zinc-finger transcriptional repressor, and ERα expression in both human breast cancer tissues and cell lines. In ERα-negative breast cancer patients, high Slug messenger RNA expression showed obviously shorter relapse-free survival. We found that Slug binds to the E-box located in the promoter of estrogen receptor 1 gene (ESR1) to suppress its expression. More specifically, Slug recruits lysine-specific demethylase 1 (LSD1) to the E-box and thereby inhibits ERα expression by demethylating H3K4me2, which is evidenced by the interaction between Slug and LSD1. Moreover, the amount of H3K4me2 binding to the E-box was significantly increased after LSD1 knockdown in MDA-MB-231 cells. Functionally, the ability to proliferate, invade and metastasize was significantly suppressed after knockdown of either Slug or LSD1 alone, or both simultaneously. Taken together, these results suggest that Slug transcriptionally inhibits ERα expression by recruiting LSD1 to the ESR1 promoter in breast cancers. Thus, targeted inhibition of Slug and LSD1 may restore ERα and lead to resensitization to hormone therapy, providing a novel therapeutic strategy for ERα-negative breast cancer patients, especially for TNBC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.