Snail represses the splicing regulator epithelial splicing regulatory protein 1 to promote epithelial-mesenchymal transition

Lauren M. Reinke, Yilin Xu, Chonghui Cheng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Epithelial-mesenchymal transition (EMT), a tightly regulated process that is critical for development, is frequently re-activated during cancer metastasis and recurrence. We reported previously that CD44 isoform switching is critical for EMT and showed that the splicing factor ESRP1 inhibits CD44 isoform switching during EMT. However, the mechanism by which ESRP1 is regulated during EMT has not been fully understood. Here we show that the transcription repressor Snail binds to E-boxes in the ESRP1 promoter, causing repression of the ESRP1 gene. Biochemically, we define the mechanism by which ESRP1 regulates CD44 alternative splicing: ESRP1 binds to the intronic region flanking a CD44 variable exon and causes increased variable exon inclusion. We further show that ectopically expressing ESRP1 inhibits Snail-induced EMT, suggesting that down-regulation of ESRP1 is required for function by Snail in EMT. Together, these data reveal how the transcription factor Snail mediates EMT through regulation of a splicing factor.

Original languageEnglish (US)
Pages (from-to)36435-36442
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number43
DOIs
StatePublished - Oct 19 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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