title: TRPM7 is required for breast tumor cell metastasis.
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.
authors.affiliation: Laboratory of Pediatric Oncology, Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Middelbeek
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Kuipers
authors.forename: Linda
authors.initials: L
authors.lastname: Henneman
authors.forename: Daan
authors.initials: D
authors.lastname: Visser
authors.forename: Ilse
authors.initials: I
authors.lastname: Eidhof
authors.forename: Remco
authors.initials: R
authors.lastname: van Horssen
authors.forename: Bé
authors.initials: B
authors.lastname: Wieringa
authors.forename: Sander V
authors.initials: SV
authors.lastname: Canisius
authors.forename: Wilbert
authors.initials: W
authors.lastname: Zwart
authors.forename: Lodewyk F
authors.initials: LF
authors.lastname: Wessels
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Peter
authors.initials: P
authors.lastname: Bult
authors.forename: Paul N
authors.initials: PN
authors.lastname: Span
authors.forename: Frank N
authors.initials: FN
authors.lastname: van Leeuwen
authors.forename: Kees
authors.initials: K
authors.lastname: Jalink
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000378:metabolism; D050053:TRPM Cation Channels / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011960:Receptors, Estrogen; D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human