Department of Gynaecology and Obstetrics, Huanggang Central Hospital of Yangtze University, Huanggang, China.
Department of Oncology, Huanggang Central Hospital of Yangtze University, No.6 Qi an Avenue, Huangzhou, Huanggang, 438000, Hubei, China.
Med Oncol. 2024 May 14;41(6):151. doi: 10.1007/s12032-024-02388-4.
Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of cancer-related death among men. A comprehensive understanding of PCa progression is crucial for the development of innovative therapeutic strategies for its treatment. While WDR1 (WD-repeat domain 1) serves as a significant cofactor of actin-depolymerizing factor/cofilin, its role in PCa progression remains unknown. In this study, we demonstrated that knockdown of WDR1 in various PCa cells substantially inhibited cell proliferation, migration, and invasion in vitro, as confirmed at both the cellular and molecular levels. Moreover, the overexpression of WDR1 promoted PCa cell proliferation and metastasis in vitro. Mechanistically, we showed that the application of lithium chloride, an activator of the Wnt/β-Catenin signaling pathway, restored the suppressive effects of WDR1 deficiency on cell proliferation and migration in PCa cells. Our findings suggest that the WDR1-β-Catenin axis functions as an activator of the malignant phenotype and represents a promising therapeutic target for PCa treatment.
前列腺癌（PCa）是男性中第二大常见癌症和第五大癌症相关死亡原因。全面了解 PCa 的进展对于开发创新的治疗策略至关重要。尽管 WD 重复域 1（WDR1）作为肌动蛋白解聚因子/原肌球蛋白的重要辅助因子，但它在 PCa 进展中的作用尚不清楚。在这项研究中，我们证明了在各种 PCa 细胞中敲低 WDR1 可显著抑制细胞增殖、迁移和侵袭，在细胞和分子水平上均得到证实。此外，过表达 WDR1 可促进 PCa 细胞在体外的增殖和转移。从机制上讲，我们表明，氯化锂（Wnt/β-Catenin 信号通路的激活剂）的应用可恢复 WDR1 缺乏对 PCa 细胞增殖和迁移的抑制作用。我们的研究结果表明，WDR1-β-Catenin 轴作为恶性表型的激活剂发挥作用，是治疗 PCa 的有前途的治疗靶点。
