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Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression

Abstract : Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This work aimed to study the role of TRPM7 in neoplastic transformation induced by cadmium exposure in non-cancer epithelial cells. Non-cancer epithelial cells were chronically exposed to low-dose of cadmium. TRPM7 expression and function were studied by Western-Blot, Patch-Clamp and calcium and magnesium imaging. Finally, cell migration and invasion were studied by Boyden chamber assays. Chronic cadmium exposure induced TRPM7 overexpression and increased the membrane currents (P < 0.001). Cells exposed to cadmium had higher intracellular calcium and magnesium levels (P < 0.05). TRPM7 silencing restored calcium levels but strongly decreased intracellular magnesium concentration (P < 0.001). Moreover, cadmium exposure enhanced both cell migration and invasion, but TRPM7 silencing strongly decreased these features (P < 0.001). Furthermore, mammary epithelial cells exposed to cadmium became rounded and had less cell-to-cell junctions. Cadmium exposure decreased epithelial markers while the mesenchymal ones were increased. Importantly, TRPM7 silencing was able to reverse these phenotypic modifications (P < 0.05). To summarize, our data show that chronic cadmium exposure enhanced TRPM7 expression and activity in non-cancer epithelial cells. TRPM7 overexpression induced intracellular magnesium increase and stimulated cell migration and invasion. These neoplastic properties could be linked to a TRPM7-dependent epithelial-to-mesenchymal transition reprogramming in cell exposed to cadmium. These findings provide new insights into the regulation of cell fates by cadmium exposure
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Contributor : Jean-Marc Ferez Connect in order to contact the contributor
Submitted on : Wednesday, April 28, 2021 - 3:31:28 PM
Last modification on : Tuesday, October 19, 2021 - 12:15:23 PM
Long-term archiving on: : Thursday, July 29, 2021 - 6:58:14 PM


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Alison Vanlaeys, Gregory Fouquet, Philippe Kischel, Frédéric Hague, Sylvie Pasco-Brassart, et al.. Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression. Archives of Toxicology, Springer Verlag, 2020, 94 (3), pp.735-747. ⟨10.1007/s00204-020-02674-w⟩. ⟨hal-02933064⟩



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