Type I collagen down-regulates E-cadherin expression by increasing PI3KCA in cancer cells

Cancer Lett. 2011 May 28;304(2):107-16. doi: 10.1016/j.canlet.2011.02.008. Epub 2011 Mar 4.

Abstract

The extracellular matrix (ECM) has been shown to induce the epithelial-mesenchymal transition (EMT), which is characterized by the loss of E-cadherin. However, little is known about the mechanisms by which collagen I, the most abundant component of ECM, induces this process. Here, we show that E-cadherin was down-regulated in response to collagen I in SKOV3 ovarian cancer cells and PC3 prostate cancer cells. Furthermore, collagen I induced the up-regulation of PIK3CA, which in turn contributed to the collagen I-induced down-regulation of E-cadherin by up-regulating its transcriptional repressors, Snail and Slug. Our data demonstrate that PIK3CA is a mediator of collagen I-induced down-regulation of E-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Collagen Type I / metabolism*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / physiology
  • Extracellular Matrix / metabolism
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Humans
  • Neoplasms / metabolism*
  • Nuclear Proteins / metabolism*
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Cadherins
  • Collagen Type I
  • Nuclear Proteins
  • PI3KCA protein, human
  • RNA, Small Interfering
  • Transcription Factors