Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China.
Department of Medical Social Services, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, China.
Cell Death Dis. 2023 Mar 10;14(3):189. doi: 10.1038/s41419-023-05694-3.
Prostate cancer poses a great threat to men's health worldwide, yet its treatment is still limited by the unclear understanding of its molecular mechanisms. CDKL3 is a molecule with a recently discovered regulatory role in human tumors, and its relationship with prostate cancer is unknown. The outcomes of this work showed that CDKL3 was significantly upregulated in prostate cancer tissues compared with adjacent normal tissues, and was significantly positively correlated with tumor malignancy. Knockdown of CDKL3 levels in prostate cancer cells significantly inhibited cell growth and migration and enhanced apoptosis and G2 arrest of the cell cycle. Cells with lower CDKL3 expression also had relatively weaker in vivo tumorigenic capacity as well as growth capacity. Exploration of downstream mechanisms of CDKL3 may regulate STAT1, which has co-expression characteristics with CDKL3, by inhibiting CBL-mediated ubiquitination of STAT1. Functionally, STAT1 is aberrantly overexpressed in prostate cancer and has a tumor-promoting effect similar to that of CDKL3. More importantly, the phenotypic changes of prostate cancer cells induced by CDKL3 were dependent on ERK pathway and STAT1. In summary, this work identifies CDKL3 as a new prostate cancer-promoting factor, which also has the potential to be a therapeutic target for prostate cancer.
前列腺癌对全球男性健康构成了巨大威胁，但由于对其分子机制的认识尚不清楚，其治疗仍然受到限制。CDKL3 是一种在人类肿瘤中具有新发现的调节作用的分子，其与前列腺癌的关系尚不清楚。这项工作的结果表明，与相邻正常组织相比，CDKL3 在前列腺癌组织中显著上调，并且与肿瘤恶性程度呈显著正相关。在前列腺癌细胞中敲低 CDKL3 水平可显著抑制细胞生长和迁移，并增强细胞凋亡和细胞周期的 G2 期阻滞。CDKL3 表达水平较低的细胞在体内的致瘤能力和生长能力也相对较弱。CDKL3 下游机制的探索可能通过抑制 CBL 介导的 STAT1 泛素化来调节具有共表达特征的 STAT1。功能上，STAT1 在前列腺癌中异常过表达，具有与 CDKL3 相似的促肿瘤作用。更重要的是，CDKL3 诱导的前列腺癌细胞的表型变化依赖于 ERK 途径和 STAT1。综上所述，这项工作确定 CDKL3 是一种新的促进前列腺癌的因素，也有可能成为前列腺癌的治疗靶点。
