Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
School of Basic Medical Science, Ningxia Medical University, Yinchuan 75004, Ningxia, China.
Aging (Albany NY). 2020 May 1;12(9):7747-7760. doi: 10.18632/aging.103085.
SPOP, a substrate binding adaptor of E3 ubiquitin ligase Cullin3, is frequently mutated in human prostate cancer (PCa). However, whether and how SPOP is regulated at transcriptional level in PCa remain unclear. Here, we report that is down-regulated in PCa stem-like cells (CSCs) and tissues. Our study reveals that SPOP expression is repressed by TGF-β / SMAD signaling axis in PCa CSCs. promoter contains SMAD-binding elements (SBEs), which can interact with SMAD3. Moreover, TGF-β signaling inhibitor SB431542 promotes the SPOP expression and abrogates PCa stemness. Clinically, SPOP expression is downregulated in PCa patients, which is significantly related to a poor prognosis and lower survival rate. Thus, our findings uncover a mechanism of how SPOP expression is mediated in PCa CSCs via TGF-β/ SMAD3 signaling.
SPOP 是 Cullin3 E3 泛素连接酶的底物结合适配器，在人类前列腺癌（PCa）中经常发生突变。然而，SPOP 是否以及如何在转录水平上在 PCa 中受到调节尚不清楚。在这里，我们报告 在 PCa 干细胞样细胞（CSCs）和组织中下调。我们的研究表明，SPOP 的表达受 PCa CSCs 中 TGF-β/SMAD 信号轴的抑制。 启动子含有 SMAD 结合元件（SBEs），可与 SMAD3 相互作用。此外，TGF-β 信号抑制剂 SB431542 促进 SPOP 的表达并消除 PCa 干性。临床上，SPOP 在前列腺癌患者中表达下调，与预后不良和生存率降低显著相关。因此，我们的研究结果揭示了 TGF-β/SMAD3 信号如何介导 PCa CSCs 中 SPOP 表达的机制。
