Antimony enhances c-Myc stability in prostate cancer via activating CtBP2-ROCK1 signaling pathway

作者：Zhang, Changwen; Lu, Chao; Wang, Zhen; Feng, Guowei; Du, E.; Liu, Yan; Wan, Li; Qiao, Baomin; Xu, Yong^*; Zhang, Zhihong^*

来源：Ecotoxicology and Environmental Safety, 2018, 164: 61-68.

DOI：10.1016/j.ecoenv.2018.07.070

• Antimony
• CtBP2
• c-Myc
• Cell proliferation
• Prostate cancer

Antimony, one of the heavier pnictogens, is widely used in industry, and its toxicity has become a major concern. Although previous studies suggested that antimony might be a tumorigenic risk factor in several cancers, the molecular basis underlying antimony-mediated transformation remains unclear. Our results showed that the serum concentration of antimony was higher in prostate cancer specimens relative to that of benign prostate tissues, and this high serum concentration of antimony was closely associated with poorer outcome in prostate cancer patients. Additionally, we demonstrated that antimony could promote prostate cancer cell growth in vitro and in vivo. In order to gain insight into the potential mechanisms, we examined the effects of antimony exposure on downstream signaling that could contribute to tumor development. We found that low-dose antimony could regulate the expression of Ctbp2 by binding and regulating the activity of its MRE domain. Meanwhile, CtBP2 could transcriptionally regulate the expression of RhoC, which is a member of the RhoGTPase family. Subsequently, the kinase activity of ROCK1 is increased, which promotes the stability of oncogene c-Myc. Overall, our study demonstrated that antimony could enhance c-Myc protein stability and promote prostate cancer cell proliferation through activating CtBP2-ROCK1 signaling pathway. These findings also substantially highlighted the potential of targeting molecules within antimony induced CtBP2-c-Myc signaling pathway as a promising therapeutic approach for the treatment of prostate cancer.

• 出版日期2018-11-30
• 单位天津医科大学