Epithelial splicing regulatory proteins 1 (ESRP1) and 2 (ESRP2) suppress cancer cell motility via different mechanisms

J Biol Chem. 2014 Oct 3;289(40):27386-99. doi: 10.1074/jbc.M114.589432. Epub 2014 Aug 20.


ESRP1 (epithelial splicing regulatory protein 1) and ESRP2 regulate alternative splicing events associated with epithelial phenotypes of cells, and both are down-regulated during the epithelial-mesenchymal transition. However, little is known about their expression and functions during carcinogenesis. In this study, we found that expression of both ESRP1 and ESRP2 is plastic: during oral squamous cell carcinogenesis, these proteins are up-regulated relative to their levels in normal epithelium but down-regulated in invasive fronts. Importantly, ESRP1 and ESRP2 are re-expressed in the lymph nodes, where carcinoma cells metastasize and colonize. In head and neck carcinoma cell lines, ESRP1 and ESRP2 suppress cancer cell motility through distinct mechanisms: knockdown of ESRP1 affects the dynamics of the actin cytoskeleton through induction of Rac1b, whereas knockdown of ESRP2 attenuates cell-cell adhesion through increased expression of epithelial-mesenchymal transition-associated transcription factors. Down-regulation of ESRP1 and ESRP2 is thus closely associated with a motile phenotype of cancer cells.

Keywords: Cancer Biology; Cell Invasion; Cell Motility; ESRP; Epithelial-Mesenchymal Transition (EMT); RNA Splicing; Rac1b; SIP1; δEF1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / physiopathology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*


  • ESRP1 protein, human
  • ESRP2 protein, human
  • RNA-Binding Proteins