An androgen-IL-6-Stat3 autocrine loop re-routes EGF signal in prostate cancer cells

Discovery of BMS-641988, a Novel and Potent Inhibitor of Androgen Receptor Signaling for the Treatment of Prostate Cancer

“…11); (d) changes in the expression ratios between AR, coactivators, and corepressors (13)(14)(15); (e) changes in the expression of enzymes involved in steroidogenesis (16); and ( f ) changes in signal transduction pathways (epidermal growth factor, insulin-like growth factor, interleukin-6, Wnt signaling, Stat5a/b, Ras/Raf/mitogenactivated protein kinase, phosphatidylinositol 3-kinase/Akt, etc.) that promote post-translational modifications (e.g., phosphorylation) of the AR and potentiate its activity under androgen-depleted conditions (17)(18)(19)(20)(21). Consistent with these observations, recent data have shown that many patients will respond to a second round of hormone therapy, confirming the critical role of the AR in HRPC and suggesting that targeting the AR with novel agents could have additional clinical benefits.…”

Androgen receptors in early and castration resistant prostate cancer: friend or foe?

“…73 Therefore, whenever stat3 is activated, for example as a response to EGF and IL6, then AR is activated. 74 e) Induction of pathways that give cells the ability to overcome androgen deprivation apoptosis. Indeed androgen ablation augments the expression of the anti-apoptotic oncogene bcl-2.…”

Inhibition of Plk1 represses androgen signaling pathway in castration-resistant prostate cancer

“…6 Some cross-talk signal transduction pathways, such as EGF pathway and IGF pathway, are upregulated and can activate AR in an androgen-independent manner. 7,8 Moreover, PCa cells can also increase expression of steroidogenic enzymes, produce androgen through de novo steroidogenesis and no longer need exogenous androgen supply. 9 The serine/threonine polo-like kinase 1 (Plk1) is a regulator of many cell cycle events, such as mitotic entry, bipolar spindle formation and cytokinesis.…”