Magnesium Research 2014; 27 (3): 103-12 REVIEW TRPM7 involvement in cancer: a potential prognostic factor Isabelle Dhennin-Duthille, Mathieu Gautier, Irina Korichneva, Halima Ouadid-Ahidouch University of Picardie Jules Verne, UFR Sciences, Laboratory of Cell and Molecular Physiology, EA 4667, SFR CAP-SANTE (FED 4231), Amiens, France Correspondence: I Dhennin-Duthille, H Ouadid-Ahidouch. University of Picardie Jules Verne, UFR Sciences, Laboratory of Cell and Molecular Physiology, EA 4667, SFR CAP-SANTE (FED 4231), Amiens, France <ha-sciences@u-picardie.fr> Abstract. Calcium (Ca 2+ ) and magnesium (Mg 2+ ) are important metal elements that regulate a variety of cellular processes such as proliferation, migration, and apoptosis, in cancer cells. Among the ionic channels mediating intracellu- lar entry, the transient receptor potential melastatin type 7 (TRPM7) channel is of particular interest, it being a non-selective, cationic channel mediating both Ca 2+ and Mg 2+ influx. TRPM7 is highly expressed in a number of human cancer tissues and cell lines. In this review, we summarise current knowledge on the physiological role of the dual function TRPM7 chanzyme, the potential application of TRPM7 as a diagnostic and prognostic marker of cancer progres- sion with respect to clinical and pathological characteristics, and the molecular mechanisms implicated in cancerogenesis that specifically involve Ca 2+ and Mg 2+ influx through TRPM7 or kinase activity and interaction with cytoskeletal proteins. Key words: TRPM7, channel activity, kinase function, proliferation, migration Cancer is one of the major causes of mor- tality worldwide, and accounted for 8.2 million deaths 2012. Cancer hallmarks include rapid and uncontrolled cell proliferation at early stages, fol- lowed by invasion of surrounding tissues and metastasis during advanced stages of the disease. Dyshomeostasis of cations is one of the features accompanying carcinogenesis. In particular, an increase in the Ca 2+ /Mg 2+ ratio is associated with higher risk of postmenopausal breast cancer [1], and high grade prostate cancer [2]. In prostate cancer cells, an increase in the Ca 2+ /Mg 2+ ratio correlates with increased Ca 2+ influx through the transient receptor potential melastatin type 7 (TRPM7) channel, and leads to enhanced prolif- eration [3]. TRPM7 is a non-selective, cationic channel per- meable to both Ca 2+ and Mg 2+ and is important for regulation of Mg 2+ homeostasis in mammals [4]. An unusual and special feature of this channel is a fused functional kinase domain at its C-terminus. The role of this kinase in TRPM7 and its relation to cancer development are gradually being eluci- dated. We herein summarize the two main functions of TRPM7 in both normal cell physiology and in cancer. The dual function TRPM7 chanzyme TRPM7 and its homolog TRPM6 are two unique, bifunctional proteins featuring a channel and an enzyme in the same polypeptide sequence and are termed “chanzymes” [5]. In 2001, TRPM7 was shown to be comprised of the TRP-PLIK (TRP phospholipase C interacting kinase) channel [6] and LTRPC7 (long TRP channel type 7) [7] in CHO-K1 and HEK-293 cell lines. The TRPM7 alpha-subunit is a ∼220 kD polypeptide that is expressed in most human tissues [7]. The TRPM7 doi:10.1684/mrh.2014.0367 103 To cite this article: Dhennin-Duthille I, Gautier M, Korichneva I, Ouadid-Ahidouch H. TRPM7 involvement in cancer: a potential prognostic factor. Magnes Res 2014; 27(3): 103-12 doi:10.1684/mrh.2014.0367