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TRPM7 对于乳腺癌细胞转移是必需的。

TRPM7 is required for breast tumor cell metastasis.

机构信息

Laboratory of Pediatric Oncology, Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.

出版信息

Cancer Res. 2012 Aug 15;72(16):4250-61. doi: 10.1158/0008-5472.CAN-11-3863. Epub 2012 Aug 7.

Abstract

TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.

摘要

TRPM7 编码一种具有激酶活性的 Ca2+通透性非选择性阳离子通道。TRPM7 被认为参与控制细胞黏附和迁移,但 TRPM7 活性是否促进癌症进展尚未确定。本文报道高水平的 TRPM7 表达可独立预测乳腺癌患者预后不良,并且在人乳腺癌的小鼠异种移植模型中,TRPM7 功能对于转移形成是必需的。机制研究表明,TRPM7 调节肌球蛋白 II 依赖的细胞张力,从而改变黏附斑数量、细胞-细胞黏附和极化细胞运动。因此,我们的研究结果表明,TRPM7 是癌细胞采用的机械敏感复合物的一部分,以驱动转移形成。

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