[FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in cultured human prostate cancer cells and its association with their invasive capability]

Zhonghua Zhong Liu Za Zhi. 2011 May;33(5):340-4.
[Article in Chinese]


Objective: To investigate the expression of heat shock protein 90 (HSP90) on the cell surface of highly invasive human prostate cancer cells PC3 and its possible molecular mechanisms of its effect on cell invasion through analyzing FAK/Src signaling pathway.

Methods: The expression of cell surface HSP90 on PC3 cells was studied by immunofluorescence staining and surface biotinylation assay respectively. A specific HSP90 antibody was used to inhibit the cell surface HSP90. In vitro cell invasion was assessed by modified Boyden chambers. Phosphorylated FAK on tyr 397, 576, 577 and 925, and phosphorylated c-Src on tyr 416 were examined by Western blot assay. The association between FAK and c-Src was analyzed by immunoprecipitation. The effects of FAK knockdown by siRNA or Src kinases inhibitor PP2, with or without anti-HSP90 antibody, on PC3 cell invasion were also evaluated.

Results: A pool of HSP90 was detected on the cell surface of PC3 cells. A specific HSP90 antibody significantly retarded tumor cell invasion. Concomitant with this finding, targeting cell surface HSP90 significantly inhibited the phosphorylations of FAK and c-Src, and also the interactions between FAK and c-Src. FAK knockdown or PP2 dramatically suppressed cell invasion, however, anti-HSP90 antibody didn't further inhibit cell invasion.

Conclusions: Cell surface HSP90 promotes human prostate cancer cell invasion through a FAK/c-Src signaling, with may be a novel therapeutic target against metastatic tumors.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Gene Knockdown Techniques
  • HSP90 Heat-Shock Proteins / immunology
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Phosphorylation
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Pyrimidines / pharmacology
  • RNA, Small Interfering / genetics
  • Signal Transduction*
  • Transfection
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / metabolism*


  • AG 1879
  • Antibodies
  • HSP90 Heat-Shock Proteins
  • Pyrimidines
  • RNA, Small Interfering
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases