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.

中文翻译：

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镉暴露通过调节的TRPM7通道表达增强细胞迁移和侵袭。

镉是涉及肿瘤转化的异种生物。镉通过二价阳离子转运蛋白进入细胞，该转运蛋白包括已知与癌细胞命运有关的瞬时受体潜在褪黑素相关7（TRPM7）。这项工作旨在研究TRPM7在非癌症上皮细胞中镉暴露诱导的肿瘤转化中的作用。非癌症上皮细胞长期暴露于低剂量的镉。通过蛋白质印迹，膜片钳和钙镁成像研究TRPM7的表达和功能。最后，通过博登室试验研究了细胞迁移和侵袭。慢性镉暴露引起TRPM7过表达并增加膜电流（P <0.001）。暴露于镉的细胞具有较高的细胞内钙和镁水平（P <0.05）。TRPM7沉默恢复了钙水平，但细胞内镁浓度大大降低（P <0.001）。此外，镉暴露增强了细胞迁移和侵袭，但TRPM7沉默大大降低了这些特征（P <0.001）。此外，暴露于镉的乳腺上皮细胞变得圆形并且具有较少的细胞间连接。镉暴露减少上皮标志物，而间充质标志物增加。重要的是，TRPM7沉默能够逆转这些表型修饰（P <0.05）。总而言之，我们的数据显示，慢性镉暴露可增强非癌症上皮细胞中TRPM7的表达和活性。TRPM7过表达诱导细胞内镁增加，并刺激细胞迁移和侵袭。这些肿瘤性质可能与暴露于镉的细胞中依赖于TRPM7的上皮-间充质转化重编程有关。这些发现为镉暴露对细胞命运的调控提供了新的见解。