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- W2323313612 abstract "Cellular transitions between epithelial and mesenchymal states have crucial roles in embryonic development and tumor metastasis. Members of the Snai1 family of zinc finger transcription factors have emerged as key regulators of epithelial-mesenchymal transition (EMT) and induce EMT in part by directly repressing epithelial markers such as E-cadherin, a gate keeper of the epithelial phenotype. However, the mechanisms underlying Snai1-mediated transcriptional repression remains incompletely understood. Our study shows Snai1 physically interacts with histone demethylase LSD1 (KDM1A) via the repressive SNAG domain located at the N-terminus. Stable over-expression of Snai1 in human mammary epithelial cell MCF10A recruits LSD1 to the E-cadherin promoter and reduce the level of dimethylation of lysine 4 in histone 3 (H3K4m2), a covalent histone modification commonly associated with active promoters. LSD1 is essential for Snai1-mediated transcriptional repression and for maintenance of the silenced state of Snai1 target genes in invasive cancer cells. In the absence of LSD1, Snai1 fails to repress E-cadherin. In cancer cells in which E-cadherin is silenced, depletion of LSD1 results in partial de-repression of epithelial genes and elevated H3K4m2 levels at the E-cadherin promoter, These results underline the critical role of LSD1 in Snai1-dependent transcriptional repression of epithelial markers and suggest that the LSD1 complex could be a potential therapeutic target for prevention of Snai1-dependent EMT and tumor invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3422. doi:10.1158/1538-7445.AM2011-3422" @default.
- W2323313612 created "2016-06-24" @default.
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- W2323313612 date "2011-04-15" @default.
- W2323313612 modified "2023-09-27" @default.
- W2323313612 title "Abstract 3422: Requirement of the histone demethylase LSD1 in Snail-mediated transcriptional repression during epithelial-mesenchymal transition" @default.
- W2323313612 doi "https://doi.org/10.1158/1538-7445.am2011-3422" @default.
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