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TGF-? signaling regulates SPOP expression and promotes prostate cancer cell stemness.


ABSTRACT: 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 SPOP is down-regulated in PCa stem-like cells (CSCs) and tissues. Our study reveals that SPOP expression is repressed by TGF-? / SMAD signaling axis in PCa CSCs. SPOP promoter contains SMAD-binding elements (SBEs), which can interact with SMAD3. Moreover, TGF-? 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-?/ SMAD3 signaling.

SUBMITTER: Jiao C 

PROVIDER: S-EPMC7244043 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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TGF-β signaling regulates <i>SPOP</i> expression and promotes prostate cancer cell stemness.

Jiao Chenchen C   Meng Tong T   Zhou Chenyu C   Wang Xinbo X   Wang Ping P   Lu Meiling M   Tan Xiao X   Wei Qing Q   Ge Xin X   Jin Jiali J  

Aging 20200501 9


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 <i>SPOP</i> 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. <i>SPOP</i> promoter contains SMAD-binding elements (SBEs), which can interact with SMAD3. Moreover  ...[more]

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2020-12-06 | GSE157496 | GEO