IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells

Biol Chem. 2012 Dec;393(12):1457-62. doi: 10.1515/hsz-2012-0209.

Abstract

The cysteine-type peptidase cathepsin X is highly upregulated in several cancers and presumably promotes tumor invasion through bypassing cellular senescence. Here, we present first evidence that the underlying mechanism may involve the regulation of the insulin-like growth factor (IGF) system, a well-known activator of proliferating tumor cells. Cathepsin X deficiency leads to a reduced phosphorylation of the IGF-I receptor in response to IGF-I stimulation. In addition, downstream signaling through focal adhesion kinase was also affected. Taken together, our results indicate that cathepsin X is able to assist in IGF signaling, which may be an important progress toward understanding cathepsin X-dependent tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin Z / genetics*
  • Cathepsin Z / metabolism
  • Cathepsins / genetics*
  • Cathepsins / metabolism
  • Cell Line, Tumor
  • Cellular Senescence
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Humans
  • Male
  • Phosphorylation
  • Prostate / cytology
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • RNA Interference
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction

Substances

  • Protein Precursors
  • Receptor, IGF Type 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Cathepsins
  • procathepsin X, human
  • CTSZ protein, human
  • Cathepsin Z