Alam Syed Mahfuzul, Rajendran Mythilypriya, Ouyang Shouqiang, Veeramani Suresh, Zhang Li, Lin Ming-Fong
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USA.
Endocr Relat Cancer. 2009 Mar;16(1):1-16. doi: 10.1677/ERC-08-0179. Epub 2008 Nov 11.
Tyrosine phosphorylation plays a critical role in growth regulation, and its aberrant regulation can be involved in carcinogenesis. The association of Shc (Src homolog and collagen homolog) adaptor protein family members in tyrosine phosphorylation signaling pathway is well recognized. Shc adaptor proteins transmit activated tyrosine phosphorylation signaling that suggest their plausible role in growth regulation including carcinogenesis and metastasis. In parallel, by sharing a similar mechanism of carcinogenesis, the steroids are involved in the early stage of carcinogenesis as well as the regulation of cancer progression and metastatic processes. Recent evidence indicates a cross-talk between tyrosine phosphorylation signaling and steroid hormone action in epithelial cells, including prostate and breast cancer cells. Therefore, the members of Shc proteins may function as mediators between tyrosine phosphorylation and steroid signaling in steroid-regulated cell proliferation and carcinogenesis. In this communication, we discuss the novel roles of Shc proteins, specifically p52(Shc) and p66(Shc), in steroid hormone-regulated cancers and a novel molecular mechanism by which redox signaling induced by p66(Shc) mediates steroid action via a non-genomic pathway. The p66(Shc) protein may serve as an effective biomarker for predicting cancer prognosis as well as a useful target for treatment.
酪氨酸磷酸化在生长调节中起关键作用，其异常调节可能参与致癌过程。Shc（Src同源物和胶原蛋白同源物）衔接蛋白家族成员在酪氨酸磷酸化信号通路中的关联已得到充分认识。Shc衔接蛋白传递激活的酪氨酸磷酸化信号，表明它们在包括致癌作用和转移在内的生长调节中可能发挥作用。同时，通过共享相似的致癌机制，类固醇参与致癌作用的早期阶段以及癌症进展和转移过程的调节。最近的证据表明，酪氨酸磷酸化信号与类固醇激素作用在上皮细胞（包括前列腺癌细胞和乳腺癌细胞）中存在相互作用。因此，Shc蛋白成员可能在类固醇调节的细胞增殖和致癌作用中充当酪氨酸磷酸化与类固醇信号之间的介质。在本通讯中，我们讨论了Shc蛋白，特别是p52(Shc)和p66(Shc)，在类固醇激素调节的癌症中的新作用，以及p66(Shc)诱导的氧化还原信号通过非基因组途径介导类固醇作用的新分子机制。p66(Shc)蛋白可能作为预测癌症预后的有效生物标志物以及治疗的有用靶点。
