TRPM7 is required for breast tumor cell metastasis

Jeroen Middelbeek, Arthur J Kuipers, Linda Henneman, Daan Visser, Ilse Eidhof, Remco van Horssen, Bé Wieringa, Sander V Canisius, Wilbert Zwart, Lodewyk F Wessels, Fred C G J Sweep, Peter Bult, Paul N Span, Frank N van Leeuwen, Kees Jalink

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4250-61
Number of pages12
JournalCancer research
Volume72
Issue number16
DOIs
Publication statusPublished - 15 Aug 2012
Externally publishedYes

Keywords

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

Fingerprint

Dive into the research topics of 'TRPM7 is required for breast tumor cell metastasis'. Together they form a unique fingerprint.

Cite this