IDENTIFYING THE VERSATILE ROLES OF NKX3.1 PHOSPHORYLATION TO EXPLORE NEW CASTRATION-RESISTANT PROSTATE CANCER THERAPY

As reported by the world health organization in 2020, prostate cancer is one of the leading forms of cancer in humans affecting approximately 191,930 men. Studies have shown that castration-resistant prostate cancer (CRPC) could develop even if the patient has undergone surgical procedures and radiotherapy. Thus, understanding the mechanism that causes CRPC could result in promising CRPC therapeutic approaches. Several approaches such as targeting Aurora A kinase, an oncogene overexpressed in multiple cancer types, have not been successful since AURKA is vital for cell survival. LIMK2 is a kinase that directly regulates AURKA and could be a better target. Recently our lab has shown that overexpression of LIMK2 results in the upregulation of AURKA and vice versa. However, five substrates of LIMK2 have been published so far amongst which 3 were identified by Shah et al. In this study, we have identified NKX3.1, a transcription factor for cell proliferation and differentiation, as a substrate of both AURKA and LIMK2. Interestingly, we have shown that overexpression of NKX 3.1 leads to downregulation of LIMK2 and AURKA. Herein, we focus on the direct communication between NKX 3.1, AURKA, and LIMK2 to develop a CRPC therapy targeting LIMK2 and NKX 3.1 as direct regulators of AURKA.