Research Paper Volume 12, Issue 9 pp 7747—7760
TGF-β signaling regulates SPOP expression and promotes prostate cancer cell stemness
- 1 Tongji University Cancer Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
- 2 Department of Pathology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
- 3 Department of Clinical Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China
- 4 School of Basic Medical Science, Ningxia Medical University, Yinchuan 75004, Ningxia, China
- 5 Cancer and Aging Research Institute, School of Life Sciences, Shandong University of Technology, Zibo 255049, Shandong, China
- 6 Department 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, 2019 Accepted: February 25, 2020 Published: May 1, 2020https://doi.org/10.18632/aging.103085
How to Cite
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.
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.