A novel splice variant of supervillin, SV5, promotes carcinoma cell proliferation and cell migration

Biochem Biophys Res Commun. 2017 Jan 1;482(1):43-49. doi: 10.1016/j.bbrc.2016.11.013. Epub 2016 Nov 5.

Abstract

Supervillin is an actin-associated protein that regulates actin dynamics by interacting with Myosin II, F-actin, and Cortactin to promote cell contractility and cell motility. Two splicing variants of human Supervillin (SV1 and SV4) have been reported in non-muscle cells; SV1 lacks 3 exons present in the larger isoform SV4. SV2, also called archvillin, is present in striated muscle; SV3, also called smooth muscle archvillin or SmAV, was cloned from smooth muscle. In the present study, we identify a novel splicing variant of Supervillin (SV5). SV5 contains a new splicing pattern. In the mouse tissues and cell lines examined, SV5 was predominantly expressed in skeletal and cardiac muscles and in proliferating cells, but was virtually undetectable in most normal tissues. Using RNAi and rescue experiments, we show here that SV5 displays altered functional properties in cancer cells, and regulates cell proliferation and cell migration.

Keywords: Alternative splicing; Cell migration; Cell proliferation; Supervillin.

MeSH terms

  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Neoplasms, Experimental / genetics*
  • Neoplasms, Experimental / metabolism
  • Organ Specificity
  • Protein Isoforms / genetics*
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Membrane Proteins
  • Microfilament Proteins
  • Protein Isoforms
  • SVIL protein, human