Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
Biochem Biophys Res Commun. 2020 Aug 27;529(3):799-804. doi: 10.1016/j.bbrc.2020.05.187. Epub 2020 Jul 20.
Prostate cancer (PCa) is the second leading cause of cancer-associated mortality in men. Speckle-type pox virus and zinc finger protein (SPOP), the most frequently mutated gene in PCa, functions as a tumor suppressor via degradation of cancer-promoting substrates. However, its upstream regulation in PCa metastasis remains poorly determined. Here, in a Snail-induced metastatic PCa model, we observed an accelerated degradation of SPOP protein in cells, which is crucial for the PCa migration and activation of the AKT signaling pathway. Mechanistically, we demonstrated that binding to Snail promoted SPOP ubiquitination and degradation. Moreover, the bric-a-brac/tramtrack/broad complex (BTB) domain of SPOP is turned out to be essential for Snail-mediated SPOP degradation. Thus, our findings reveal a post-translational level regulation of SPOP expression that facilitates the metastasis of PCa cells.
前列腺癌（PCa）是男性癌症相关死亡的第二大主要原因。斑点状痘病毒和锌指蛋白（SPOP）是 PCa 中最常突变的基因，通过降解致癌底物发挥肿瘤抑制作用。然而，其在 PCa 转移中的上游调控仍不清楚。在这里，在 SNAI 诱导的转移性 PCa 模型中，我们观察到细胞中 SPOP 蛋白的降解加速，这对于 PCa 的迁移和 AKT 信号通路的激活至关重要。从机制上讲，我们证明了与 SNAI 的结合促进了 SPOP 的泛素化和降解。此外，SPOP 的 bric-a-brac/tramtrack/broad complex（BTB）结构域对于 SNAI 介导的 SPOP 降解是必不可少的。因此，我们的研究结果揭示了 SPOP 表达的翻译后水平调控，促进了 PCa 细胞的转移。
