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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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

Lauren M Reinke1, Yilin Xu, Chonghui Cheng

  • 1Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

The Journal of Biological Chemistry
|September 11, 2012
PubMed

Insights

The transcription factor Snail represses the splicing factor ESRP1, which is crucial for regulating CD44 during epithelial-mesenchymal transition (EMT). This reveals a novel mechanism controlling EMT progression in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Epithelial-mesenchymal transition (EMT) is vital for development and often reactivated in cancer metastasis.
  • CD44 isoform switching is critical for EMT, and the splicing factor ESRP1 inhibits this switch.
  • The regulatory mechanism of ESRP1 during EMT remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism by which ESRP1 is regulated during EMT.
  • To define how ESRP1 influences CD44 alternative splicing.
  • To investigate the role of Snail in regulating ESRP1 and EMT.

Main Methods:

  • Analysis of Snail binding to the ESRP1 promoter using E-boxes.
  • Biochemical characterization of ESRP1's interaction with the CD44 gene.
  • Experimental manipulation of ESRP1 expression to assess its effect on Snail-induced EMT.

Main Results:

  • The transcription repressor Snail directly binds to ESRP1 promoter E-boxes, leading to gene repression.
  • ESRP1 binds intronic regions flanking CD44 variable exons, promoting their inclusion.
  • Ectopic ESRP1 expression inhibits Snail-induced EMT, indicating ESRP1 downregulation is necessary for Snail's function.

Conclusions:

  • Snail-mediated repression of ESRP1 is a key mechanism controlling EMT.
  • The Snail-ESRP1-CD44 axis represents a novel regulatory pathway in EMT.
  • Understanding this pathway offers potential therapeutic targets for preventing cancer metastasis and recurrence.

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