Figure 5.

A proposed scheme of steroid-regulated cancer progression via Shc proteins. Upon steroid activation, p52^Shc undergoes phosphorylation at Y317 and promotes tumor growth at least in part via transducing signals through the Grb2–Ras–MAPK pathway. Like p52^Shc, p66^Shc protein also promotes tumor progression, nevertheless, via mediating oxidative stress signals through the generation of ROS. Upon stimulation by steroids, p66^Shc is translocated to mitochondria via Ser-36 phosphorylation-independent manner resulting in the generation of ROS. ROS may then inhibit PTP, resulting in RPTK activation, ERK/MAPK activation, and promote cell proliferation, survival, and migration, which collectively lead to metastasis.