TRPM7 drives breast cancer metastasis
Changes in the ability of cells to adhere to other cells or their cellular environment are central to tumor cell metastasis. The cation channel TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been investigated. In a study published this month in Cancer Research, researchers of the Laboratory of Pediatric Oncology, the Department of Radiotherapy and the Netherlands Cancer Institute evaluated whether expression of the TRPM7 gene correlated with breast cancer progression. In primary breast tumors, removed at diagnosis from a cohort of 368 women, high levels of expression from the TRPM7 gene were associated with significantly shorter times to both disease recurrence and occurrence of distant metastases. This association was validated in an independent cohort of 144 breast cancer patients. In addition the authors showed using a mouse model, that loss of TRPM7 expression efficiently blocks metastatic spread of breast cancer cells in vivo, while affecting cell adhesion and migration in the cultured breast cancer cells. Although these findings will not have an immediate impact on patient care, it opens the door to a previously under-explored area of cancer therapeutics. Being a cation channel, TRPM7 belongs to a class of proteins that is already therapeutically targeted to treat diseases; for example, cation channel blockers are used to treat several cardiovascular diseases. Given that cation channels are druggable, these data provide clear rationale for probing whether drugs that target this class of proteins can be used to block metastasis formation in cancer patiënts. This study was supported by grants from the Dutch Cancer Society (KWF). An official press release on this topic was published by the American Association for Cancer Research on August 7. For more information visit www.AACR.org.
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 http://cancerres.aacrjournals.org/content/early/2012/07/31/0008-5472.CAN-11-3863.full.pdf+html
Photo: Jeroen Middelbeek
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