p66Shc--a longevity redox protein in human prostate cancer progression and metastasis : p66Shc in cancer progression and metastasis.
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.
Rajendran
Mythilypriya
M
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Thomes
Paul
P
Zhang
Li
L
Veeramani
Suresh
S
Lin
Ming-Fong
MF
D000818:Animals; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D010084:Oxidation-Reduction; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D000090063:Proto-Oncogene Mas; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1