p66Shc--a longevity redox protein in human prostate cancer progression and metastasis : p66Shc in cancer progression and metastasis

Cancer Metastasis Rev. 2010 Mar;29(1):207-22. doi: 10.1007/s10555-010-9213-8.

Abstract

p66Shc, a 66 kDa proto-oncogene Src homologous-collagen homologue (Shc) adaptor protein, is classically known in mediating receptor tyrosine kinase signaling and recently identified as a sensor to oxidative stress-induced apoptosis and as a longevity protein in mammals. The expression of p66Shc is decreased in mice and increased in human fibroblasts upon aging and in aging-related diseases, including prostate cancer. p66Shc protein level correlates with the proliferation of several carcinoma cells and can be regulated by steroid hormones. Recent advances point that p66Shc protein plays a role in mediating cross-talk between steroid hormones and redox signals by serving as a common convergence point in signaling pathways on cell proliferation and apoptosis. This article first reviews the unique function of p66Shc protein in regulating oxidative stress-induced apoptosis. Subsequently, we discuss its novel role in androgen-regulated prostate cancer cell proliferation and metastasis and the mechanism by which it mediates androgen action via the redox signaling pathway. The data together indicate that p66Shc might be a useful biomarker for the prognosis of prostate cancer and serve as an effective target for its cancer treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • Carcinoma / therapy
  • Disease Progression
  • Humans
  • Longevity / genetics*
  • Male
  • Mice
  • Models, Biological
  • Neoplasm Metastasis
  • Oxidation-Reduction
  • Prognosis
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / therapy
  • Shc Signaling Adaptor Proteins / genetics
  • Shc Signaling Adaptor Proteins / metabolism
  • Shc Signaling Adaptor Proteins / physiology*
  • Src Homology 2 Domain-Containing, Transforming Protein 1

Substances

  • SHC1 protein, human
  • Shc Signaling Adaptor Proteins
  • Src Homology 2 Domain-Containing, Transforming Protein 1