Author(s):
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Middelbeek, J.A.J.
;
Kuipers, A.J.
; Henneman, L.; Visser, D.; Eidhof, I.;
Horssen, R. van
;
Wieringa, B.
; Canisius, S.V.M.; Zwart, W.; Wessels, L.F.;
Sweep, C.G.J.
;
Bult, P.
;
Span, P.N.
;
Leeuwen, F.N. van
; Jalink, K.
|
Subject:
|
IGMD 6: Hormonal regulation ONCOL 5: Aetiology, screening and detection NCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicine ONCOL 2: Age-related aspects of cancer ONCOL 2: Age-related aspects of cancer NCMLS 2: Immune Regulation ONCOL 3: Translational research |
Organization:
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Paediatrics Laboratory of Genetic, Endocrine and Metabolic Diseases Cell Biology (UMC) Pathology Radiation Oncology |
Abstract:
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TRPM7 encodes a Ca(2+)-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. Cancer Res; 72(16); 4250-61. (c)2012 AACR.
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