Steroid receptor coactivator-3/AIB1 promotes cell migration and invasiveness through focal adhesion turnover and matrix metalloproteinase expression

Cancer Res. 2008 Jul 1;68(13):5460-8. doi: 10.1158/0008-5472.CAN-08-0955.

Abstract

Steroid receptor coactivator-3 (SRC-3)/AIB1 is a member of the p160 nuclear receptor coactivator family involved in development and cell cycle progression. We previously showed that SRC-3/AIB1 is required for prostate cancer cell proliferation and survival. Here, we reported that the elevated SRC-3/AIB1 expression is significantly correlated with human prostate cancer seminal vesicle invasion and lymph node metastasis. Furthermore, SRC-3/AIB1 is associated with increased prostate cancer cell migration and invasion. SRC-3/AIB1 is required for focal adhesion turnover and focal adhesion kinase activation. In addition, SRC-3/AIB1 directly regulates transcription of matrix metalloproteinase (MMP)-2 and MMP-13 through its coactivation of AP-1 and PEA3. Taken together, these data suggest that SRC-3/AIB1 plays an essential role in prostate cancer cell invasion and metastasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Movement / genetics*
  • Focal Adhesion Kinase 1 / metabolism
  • Focal Adhesions / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 13 / physiology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / physiology
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Nuclear Receptor Coactivator 3
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Signal Transduction / genetics
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tumor Cells, Cultured

Substances

  • Transcription Factor AP-1
  • Transcription Factors
  • transcription factor PEA3
  • Nuclear Receptor Coactivator 3
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2