KIF20A Facilitates Prostate Cancer Proliferation and Docetaxel Resistance via Enhancing USP15-Dependent K63-linked deubiquitination of G3BP1

Abstract Although our previous study implied that kinesin family member 20A (KIF20A) is frequently up-regulated in prostate cancer (PCa) and links to poor survival, the roles and mechanism remain largely poor understood. In this study, we further reported that KIF20A overexpressed in PCa and docetaxel resistance cells, and predicted unfavorable prognosis. Moreover, KIF20A accelerated the PCa cells proliferation and conferred resistance to docetaxel in vitro and in vivo. A mechanistic study revealed that KIF20A promotes PCa progression by activating β-catenin pathway. Furthermore, KIF20A physically interacted with USP15, a crucial deubiquitinating enzyme to catalyze K-63 linked deubiquitination of K393 and K495 lysine resident of G3BP1, thus up-regulated G3BP1 activated β-catenin subsequently. Altogether, our study revealed the clinical significance of KIF20A in PCa, and implied that targeting KIF20A might be a promising strategy to delay the PCa proliferation and overcome docetaxel resistance.