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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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https://hal.univ-reims.fr/hal-03010068
Contributor : Jean-Marc Ferez Connect in order to contact the contributor
Submitted on : Tuesday, December 15, 2020 - 11:18:47 AM
Last modification on : Thursday, October 14, 2021 - 1:10:08 PM
Long-term archiving on: : Tuesday, March 16, 2021 - 7:15:51 PM

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Alison Vanlaeys, Grégory 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-03010068⟩

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