Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway

Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):251-5. doi: 10.1016/j.bbrc.2014.10.154. Epub 2014 Nov 6.

Abstract

Vinculin regulates a variety of cellular functions partly through stabilization of tumor suppressor PTEN. In order to study the role of vinculin in tumor progression other than PTEN stabilization, vinculin was knocked down in PTEN-deficient squamous cell carcinoma HSC-4 cells. Knockdown of vinculin induced phenotypical change by reducing cell-cell and cell-extracellular matrix adhesions, and enhanced MT1-MMP expression at transcription level and subsequent cell migration. Up-regulation of MT1-MMP transcription by vinculin knockdown was abrogated by ERK inhibition. These results suggest that vinculin negatively regulates malignant phenotype of tumor cells including MT1-MMP transcription through MEK/ERK pathway.

Keywords: Cancer; Cell–extracellular matrix adhesion; MT1-MMP; Migration; Vinculin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Cell Line, Tumor
  • Cell Movement
  • Collagen / metabolism
  • Enzyme Activation
  • Extracellular Matrix / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • MAP Kinase Signaling System*
  • Matrix Metalloproteinase 14 / metabolism*
  • Phenotype
  • Prognosis
  • RNA, Small Interfering / metabolism
  • Transcription, Genetic
  • Vinculin / metabolism*

Substances

  • RNA, Small Interfering
  • VCL protein, human
  • Vinculin
  • Collagen
  • Extracellular Signal-Regulated MAP Kinases
  • MMP14 protein, human
  • Matrix Metalloproteinase 14