TRPM7 is required for breast tumor cell metastasis

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Adhesion / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cytoskeleton / drug effects
  • Cytoskeleton / pathology
  • Disease Progression
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / metabolism
  • TRPM Cation Channels / biosynthesis*
  • TRPM Cation Channels / deficiency
  • TRPM Cation Channels / genetics

Substances

  • RNA, Messenger
  • Receptors, Estrogen
  • TRPM Cation Channels
  • Protein-Serine-Threonine Kinases
  • TRPM7 protein, human