TY - JOUR
T1 - Cadmium induces epithelial–mesenchymal transition and migration of renal cancer cells by increasing PGE2 through a cAMP/PKA-COX2 dependent mechanism
AU - Shi, Haifeng
AU - Sun, Xi
AU - Kong, Anqi
AU - Ma, Haiyan
AU - Xie, Yimin
AU - Cheng, Dongrui
AU - Wong, Chris K C
AU - Zhou, Yang
AU - Gu, Jie
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China ( 31600952 and 31271272 ), the Foundation of Health and Family Planning Commission of Wuxi ( Q201807 and MS201812 ), and the Start-Up Research Funding of Jiangsu University for Distinguished Scholars ( 5501330001 ). We thank the anonymous reviewer for the comments on the roles of PGE2.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Cadmium
KW - Epithelial-mesenchymal transition
KW - Migration
KW - Prostaglandin E2
KW - Renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85094562005&partnerID=8YFLogxK
U2 - 10.1016/j.ecoenv.2020.111480
DO - 10.1016/j.ecoenv.2020.111480
M3 - Journal article
C2 - 33254385
AN - SCOPUS:85094562005
SN - 0147-6513
VL - 207
JO - Ecotoxicology and Environmental Safety
JF - Ecotoxicology and Environmental Safety
M1 - 111480
ER -
