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.
©2012 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology*
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Cell Adhesion / physiology
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Cell Line, Tumor
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Cell Movement / physiology
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Cytoskeleton / drug effects
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Cytoskeleton / pathology
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Disease Progression
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Female
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Gene Knockdown Techniques
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Humans
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Mice
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Mice, Transgenic
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Neoplasm Metastasis
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Neoplasm Staging
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Protein Serine-Threonine Kinases
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Receptors, Estrogen / biosynthesis
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Receptors, Estrogen / metabolism
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TRPM Cation Channels / biosynthesis*
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TRPM Cation Channels / deficiency
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TRPM Cation Channels / genetics
Substances
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RNA, Messenger
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Receptors, Estrogen
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TRPM Cation Channels
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Protein Serine-Threonine Kinases
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TRPM7 protein, human