Snail-mediated Cripto-1 repression regulates the cell cycle and epithelial-mesenchymal transition-related gene expression

FEBS Lett. 2015 May 8;589(11):1249-56. doi: 10.1016/j.febslet.2015.04.005. Epub 2015 Apr 15.

Abstract

Transcription factor Snail mediates epithelial to mesenchymal transitions (EMT) by coordinate repression of epithelial markers, facilitating mass cell movement during germ layer formation. Aberrant reprogramming in its signaling pathways causes metastatic cancer. Snail's involvement in "fate-changing" decisions is however not understood. Cripto-1 shares a common temporal expression pattern with Snail during development. While Cripto-1 is required for mammary morphogenesis and hematopoietic stem cell renewal, its unregulated expression causes metastatic cancers. Therefore, we suspected that Snail regulates the expression of Cripto-1 controlling decisions such as motility, transformation and differentiation. We demonstrate that Snail represses Cripto-1 gene by direct transcriptional interaction and propose a novel mechanism by which it co-ordinately regulates cell fate decisions during development and could be causal of cancers.

Keywords: Cripto-1; Epithelial–mesenchymal transition; Snail; Transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Epithelial-Mesenchymal Transition / physiology*
  • GPI-Linked Proteins / biosynthesis*
  • GPI-Linked Proteins / genetics
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / physiology*

Substances

  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Repressor Proteins
  • Snail Family Transcription Factors
  • TDGF1 protein, human
  • Transcription Factors