PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin

Exp Cell Res. 2018 Aug 1;369(1):158-165. doi: 10.1016/j.yexcr.2018.05.018. Epub 2018 May 19.


Cell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho-associated protein kinase (ROCK), LIM-Kinase (LIMK), and cofilin. Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. In this study, we discovered that PRP4 over-expression in HCT116 colon cancer cells induces cofilin dephosphorylation by inhibiting the Rho-ROCK-LIMK-cofilin pathway. Two-dimensional gel electrophoresis, and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4-transfected HCT116 cells. The presence of PRP4 increased the expression of PP1A both at the mRNA and protein levels, which possibly activated cofilin through dephosphorylation and subsequently modulated the cell actin cytoskeleton. Furthermore, we found that PRP4 over-expression did not induce cofilin dephosphorylation in the presence of okadaic acid, a potent phosphatase inhibitor. Moreover, we discovered that PRP4 over-expression in HCT116 cells induced dephosphorylation of migration and invasion inhibitory protein (MIIP), and down-regulation of E-cadherin protein levels, which were further restored by the presence of okadaic acid. These findings indicate a possible molecular mechanism of PRP4-induced actin cytoskeleton remodeling and epithelial-mesenchymal transition, and make PRP4 an important target in colon cancer.

Keywords: Actin cytoskeleton; Cofilin; EMT; Pre-mRNA processing factor 4B (PRP4); Protein Phosphatase 1A (PP1A).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism*
  • Actin Depolymerizing Factors / metabolism*
  • Actins / metabolism*
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • HCT116 Cells
  • Humans
  • Lim Kinases / metabolism
  • Neoplasm Invasiveness
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism
  • Ribonucleoprotein, U4-U6 Small Nuclear / physiology*
  • Signal Transduction
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • Actin Depolymerizing Factors
  • Actins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • LIMK1 protein, human
  • Lim Kinases
  • PRPF4B protein, human
  • Protein-Serine-Threonine Kinases
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein