Figure 3. Therapeutic targeting of Stat5a/b inhibits growth of prostate cancer through AR-dependent and AR-independent mechanisms.

Disruption of Stat5a/b signaling inhibits growth and viability of prostate cancer through two distinct mechanisms, serving as a potential dual strategy to eliminate prostate cancer cells. First, targeting of Stat5a/b inhibits the abilities of Stat5a/b to protect antiandrogen-liganded AR from proteasomal degradation and enhance AR signaling, including downstream molecular events such as AR nuclear localization, chromatin binding, and activation of target gene expression in prostate cancer cells. Second, targeting of Stat5a/b prevents the induction of AR-independent, Stat5a/b-regulated genes involved in proliferation and survival of prostate cancer cells.