Sun Baisheng, Long Yin, Xiao Ling, Wang Jiazhi, Yi Qian, Tong Dali, Li Ke
Emergency Department, The Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing 100071, China.
Department of Urology, Daping Hospital, Army Medical University, Chongqing 400042, China.
J Oncol. 2022 Apr 11;2022:6085948. doi: 10.1155/2022/6085948. eCollection 2022.
The activation of the androgen receptor (AR) pathway is crucial in the progression of human prostate cancer. Results of the present study indicated that the target protein xenopus kinesin-like protein (TPX2) enhanced the transcription activation of AR and promoted the proliferation of LNCaP (ligand-dependent prostate carcinoma) cells. The protein-protein interaction between AR and TPX2 was investigated using coimmunoprecipitation assays. Results of the present study further demonstrated that TPX2 enhanced the transcription factor activation of AR and enhanced the expression levels of the downstream gene prostate-specific antigen (PSA). TPX2 did this by promoting the accumulation of AR in the nucleus and also promoting the recruitment of AR to the androgen response element, located in the promoter region of the PSA gene. Overexpression of TPX2 enhanced both the in vitro and in vivo proliferation of LNCaP cells. By revealing a novel role of TPX2 in the AR signaling pathway, the present study indicated that TPX2 may be an activator of AR and thus exhibits potential as a novel target for prostate carcinoma treatment.
雄激素受体（AR）信号通路的激活在人类前列腺癌进展过程中至关重要。本研究结果表明，靶蛋白非洲爪蟾驱动蛋白样蛋白（TPX2）增强了AR的转录激活，并促进了LNCaP（激素依赖型前列腺癌）细胞的增殖。使用免疫共沉淀试验研究了AR与TPX2之间的蛋白质-蛋白质相互作用。本研究结果进一步证明，TPX2增强了AR的转录因子激活，并提高了下游基因前列腺特异性抗原（PSA）的表达水平。TPX2通过促进AR在细胞核中的积累以及促进AR募集至位于PSA基因启动子区域的雄激素反应元件来实现这一点。TPX2的过表达增强了LNCaP细胞的体外和体内增殖。通过揭示TPX2在AR信号通路中的新作用，本研究表明TPX2可能是AR的激活剂，因此具有作为前列腺癌治疗新靶点的潜力。
