β6 integrin induces the expression of metalloproteinase-3 and metalloproteinase-9 in colon cancer cells via ERK-ETS1 pathway

Cancer Lett. 2014 Nov 28;354(2):427-37. doi: 10.1016/j.canlet.2014.08.017. Epub 2014 Aug 15.

Abstract

We previously reported that β6 integrin played an important role in the progression of colon cancer. In this study, we demonstrated that β6 integrin induced the expression of MMP-3/MMP-9 and the invasion of colon cancer cells. Moreover, that function was abolished by the inhibition of ERK/MAPK pathways or knockdown of ETS1, an important transcription factor of MMP genes. Here, we showed that β6 induced phosphorylation of ETS1 via the ERK/MAPK pathways, through which the MMP-3/MMP-9 promoters were stimulated, thereby leading to the up-regulation of MMP-3/MMP-9, and subsequent the invasion of colon cancer cells.

Keywords: Colon cancer; ETS1; β6 integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • HT29 Cells
  • Humans
  • Integrin beta Chains / biosynthesis
  • Integrin beta Chains / genetics
  • Integrin beta Chains / metabolism*
  • MAP Kinase Signaling System*
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Molecular Sequence Data
  • Phosphorylation
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • ETS1 protein, human
  • Integrin beta Chains
  • Proto-Oncogene Protein c-ets-1
  • RNA, Messenger
  • integrin beta6
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • MMP9 protein, human
  • Matrix Metalloproteinase 9