Cadmium induces epithelial-mesenchymal transition and migration of renal cancer cells by increasing PGE2 through a cAMP/PKA-COX2 dependent mechanism

被引:29
作者
Shi, Haifeng [1 ]
Sun, Xi [1 ]
Kong, Anqi [1 ]
Ma, Haiyan [1 ]
Xie, Yimin [2 ]
Cheng, Dongrui [3 ]
Wong, Chris Kong Chu [4 ]
Zhou, Yang [1 ]
Gu, Jie [1 ]
机构
[1] Jiangsu Univ, Sch Life Sci, Xuefu Rd 301, Zhenjiang 212000, Jiangsu, Peoples R China
[2] Jiangsu Univ, Yixing Hosp, Affiliated Hosp, Yixing 214200, Jiangsu, Peoples R China
[3] Gen Hosp Nanjing Mil Reg, East Zhongshan Rd 305, Nanjing 210002, Jiangsu, Peoples R China
[4] Hong Kong Baptist Univ, Dept Biol, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
Cadmium; Epithelial-mesenchymal transition; Migration; Prostaglandin E2; Renal cell carcinoma; CADHERIN CLEAVAGE; PROSTAGLANDIN E-2; COX-2; EXPRESSION; TRACE-ELEMENTS; CAMP; INVOLVEMENT; ACTIVATION; AUTOPHAGY; INVASION; RECEPTOR;
D O I
10.1016/j.ecoenv.2020.111480
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Environmental or occupational exposure of Cadmium (Cd) is concerned to be a threat to human health. The kidney is main target of Cd accumulation, which increases the risk of renal cell carcinoma (RCC). In addition, low content of Cd had been determined in kidney cancer, however, the roles of presence of Cd in renal tumors progression are still unclear. The present study is proposed to determine the effect of low-dose Cd exposure on the renal cancer cells and aimed to clarify the underlying mechanisms. The cell viability, cytotoxicity, and the migratory effect of low-dose Cd on the renal cancer cells were detected. Moreover, the roles of reactive oxygen species (ROS), Ca2+, and cyclic AMP (cAMP)/protein kinase A (PKA)-cyclooxygenase2 (COX2) signaling, as well as COX2 catalytic product prostaglandin E2 (PGE2) on cell migration and invasion were identified. Our results suggested that low dose Cd exposure promoted migration of renal cancer Caki-1 cells, which was not dependent on Cd-induced ROS and intracellular Ca2+ levels. Cd exposure induced cAMP/PKA-COX2, which mediated cell migration and invasion, and decreased expressions of epithelial-mesenchymal transition (EMT) marker, E-cadherin, but increased expressions of N-cadherin and Vimentin. Moreover, Cd-induced secretion of PGE2 feedback on activation of cAMP/PKA-COX2 signaling, also promoted EMT, migration and invasion of renal cancer Caki-1 cells. This study might contribute to understanding of the mechanism of Cd-induce progression of renal cancer and future studies on the prevention and therapy of renal cell carcinomas.
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页数:9
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