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

Haifeng Shi, Xi Sun, Anqi Kong, Haiyan Ma, Yimin Xie, Dongrui Cheng, Chris K C WONG, Yang Zhou, Jie Gu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number111480
JournalEcotoxicology and Environmental Safety
Volume207
DOIs
Publication statusPublished - 1 Jan 2021

Scopus Subject Areas

  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

User-Defined Keywords

  • Cadmium
  • Epithelial-mesenchymal transition
  • Migration
  • Prostaglandin E2
  • Renal cell carcinoma

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