Organelles Ca ²⁺ redistribution contributes to cadmium-induced EMT of renal cancer cells through p-cPLA 2 -mediated arachidonic acid release.

Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2025 Jun 15; Vol. 298, pp. 118317. Date of Electronic Publication: 2025 May 17.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Cadmium ion (Cd ²⁺ ) is a non-essential metal that can increase cancer risk, including potentially renal cell carcinoma (RCC), though this link is not definitive. Cd ²⁺ exposure impairs fatty acid metabolism in the kidneys, particularly affecting arachidonic acid (AA) levels, which are crucial for health. Previous studies have suggested that Cd ²⁺ -altered the AA metabolism associates with renal dysfunction. However, the role and mechanism of Cd ²⁺ -regulated AA source in promoting RCC progression are still unclear. This study aims to investigate how Cd ²⁺ exposure affects AA levels in renal cancer cells and its role in promoting cell migration. Cd ²⁺ exposure increases AA levels through cPLA 2 -mediated release. It also induces calcium ion (Ca ²⁺ ) redistribution from the endoplasmic reticulum (ER) to mitochondria, activating the p38 MAPK/cPLA 2 signaling pathway, and epithelial-mesenchymal transition (EMT) of Caki-1 cells. Cd ²⁺ -induced ER Ca ²⁺ release, p38 MAPK/cPLA 2 signaling activation, AA levels, and EMT of Caki-1 cells were effectively reversed by siRNA knockdown of IP3R. Both exogenous AA treatments and Cd ²⁺ -induced AA metabolite PGD2 promoted EMT and cell migration of Caki-1 cells. This study highlights Cd ^2+' s impact on fatty acid metabolism and organelle function in renal cancer cells, identifying potential therapeutic targets for RCC.
(Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

English

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7805381 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2414 (Electronic) Linking ISSN: 01476513 NLM ISO Abbreviation: Ecotoxicol Environ Saf Subsets: MEDLINE

Arachidonic Acid*/metabolism , Epithelial-Mesenchymal Transition*/drug effects , Cadmium*/toxicity , Calcium*/metabolism , Kidney Neoplasms*/metabolism , Phospholipases A2, Cytosolic*/metabolism, Humans ; Cell Line, Tumor ; Cell Movement/drug effects ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/drug effects

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