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

p66Shc in cancer progression and metastasis

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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.

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Acknowledgement

This study was supported in part by National Cancer Institute, National Institutes of Health [R01 CA88184], Department of Defense [W81XWH-06-1-0070 and W81XWH-08-1-0459], Nebraska Research Initiative for Cancer Metastasis, and Nebraska Cancer and Smoking Disease Research Program LB 506 [2008-20 and 2010-18]. We thank Dr. Shouqiang Ouyang for reading, and Ms. Fen-Fen Lin for her tremendous contributions toward our studies on the functional role of p66Shc in carcinogenesis.

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  1. Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Mythilypriya Rajendran, Paul Thomes, Li Zhang, Suresh Veeramani & Ming-Fong Lin

  2. Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Ming-Fong Lin

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  1. Mythilypriya Rajendran
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Correspondence to Ming-Fong Lin.

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Rajendran, M., Thomes, P., Zhang, L. et al. p66Shc—a longevity redox protein in human prostate cancer progression and metastasis. Cancer Metastasis Rev 29, 207–222 (2010). https://doi.org/10.1007/s10555-010-9213-8

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