Activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as TNK2, tyrosine kinase non-receptor 2) binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs.
ACK1 has been shown to interact with AKT, Androgen receptor or AR, tumor suppressor WWOX, FYN and Grb2. ACK1 has been shown to be critical for progression of PC to hormone therapy insensitive stage called castration resistant prostate cancer or CRPC due to it’s ability to regulate the expression and function of AR in androgen-independent manner.
The ACK1 inhibitor (R)-9bMS sensitized naive and enzalutamide-resistant prostate cancer cells and reduced AR and AR-V7 levels to mitigate CRPC tumor growth.
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