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Research Paper|Volume 12, Issue 9|pp 7747—7760

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

Chenchen Jiao1, Tong Meng1, Chenyu Zhou1, Xinbo Wang1, Ping Wang1,4,5, Meiling Lu6, Xiao Tan1, Qing Wei2, Xin Ge3, Jiali Jin1,4
  • 1Tongji University Cancer Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
  • 2Department of Pathology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
  • 3Department of Clinical Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
  • 4School of Basic Medical Science, Ningxia Medical University, Yinchuan 75004, Ningxia, China
  • 5Cancer and Aging Research Institute, School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong, China
  • 6Department of Central Laboratory, School of Life Science and Technology, Shanghai Tenth People's Hospital of Tongji University, Tongji University, Shanghai 200072, China
Received: October 24, 2019Accepted: February 25, 2020Published: May 1, 2020

Copyright © 2020 Jiao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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-β / SMAD signaling axis in PCa CSCs. SPOP 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.