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.