We recently showed that the melastatin-like transient receptor potential 7 (TRPM7) channel regulates cell proliferation in the estrogen receptor positive (ER+) non-invasive MCF-7 human breast cancer cell line (Guilbert et al., 2009). Here, we aimed to determine the role and expression of TRPM7 channels in ER- invasive ductal carcinoma (IDC) which is the most aggressive form of breast cancer. TRPM7 is implicated in various cellular processes related to cell motility (Clark et al., 2006; Su et al., 2006), however, its role in IDC is far to be understood. The TRPM7 expression in invasive areas of human IDC surgical specimens was assessed using immunohistochemistry. The functional expression of TRPM7 was also recorded in the ER- highly metastatic breast cancer cell line, MDA-MB-231, using patch-clamp and Ca2+/Mg2+ imaging. Finally, the role of TRPM7 in proliferation, adhesion and migration of MDA-MB-231 was evaluated using specific TRPM7 silencing by the siRNA technique. Results are presented as mean ± S.E.M. and statistics were performed using Mann-Whitney test. Analysis of ER- IDC samples by immunohistochemistry showed that TRPM7 channels were expressed at a higher level in invasive areas when compared to the non-invasive areas. In the ER- metastatic breast cancer cell line, MDA-MB-231, a Magnesium Inhibited Cation (MIC) current was activated by the whole-cell dialysing with a 0 free Mg intrapipette solution. The MIC current exhibited a maximal current-density of 9.6 ± 0.2 pA/pF at +100 mV (n=9) and was inhibited by increasing internal free Mg2+ to 6.3 mM (2.9 ± 0.3 pA/pF at +100 mV, n=5, P<0.05). Moreover, the MIC current was also almost completely inhibited by TRPM7 silencing (4.1 ± 0.9 pA/pF at +100 mV, n=8 in siTRPM7 condition compared to 6.7 ± 0.8 pA/pF at +100 mV, n=10 in siControl condition; P<0.05) suggesting that TRPM7 channels support the MIC current in MDA-MB-231 cell line. Neither Ca2+, Mg2+-homeostasis nor cell proliferation were affected by siTRPM7 in MDA-MB-231 cell line. However, siTRPM7 decreased the number of adherent cells by 20.0 ± 2.3% (P<0.05) and strongly inhibited the migration by 67.9 ± 2.7% (P<0.05) in MDA-MB-231 cell line. Taken together, these results suggest that TRPM7 modulates adhesion and migration of MDA-MB-231 breast cancer cells without affecting cell proliferation. Importantly, TRPM7 is expressed at a higher level in invasive areas of the more aggressive ER- human IDC. TRPM7 channel may be a biomarker of clinically aggressive IDC.