Evidence that TRPM7 is required for breast cancer cell proliferation

Abstract

Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg(2+)-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg(2+) or Mg(2+)-ATP. The inward current was reduced by La(3+), and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La(3+), and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca(2+) concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca(2+) influx.

The Role of Waixenicin A as Transient Receptor Potential Melastatin 7 Blocker

“…In addition, they suggested that this channel be viewed as a potential target for the pharmacological treatment of gastric cancer. Guilbert et al [10] also suggested that TRPM7 is required for breast cancer cell proliferation. In the present study, we found waixenicin A inhibited cell viability ( fig.…”

“…Guilbert et al [10] suggested that TRPM7 contributes to the proliferative potential of breast cancer (MCF-7) cells. Therefore, we investigated the influence of waixenicin A on MCF-7 survival.…”

“…We previously suggested that TRPM7 is a primary molecular candidate for the NSCC responsible for ICC pacemaking activity in the murine small intestine [8], and thus, we view TRPM7 as a promising new target for the pharmacological treatment of GI motility disorders. Furthermore, others have suggested that human gastric and breast adenocarcinoma cells express TRPM7 channel and its expression is essential for cell survival, and thus, this TRPM7 channel is also a potential therapeutic target in gastric and breast cancer [9,10].…”

Effects of Transient Receptor Potential Channel Blockers on Pacemaker Activity in Interstitial Cells of Cajal from Mouse Small Intestine

“…TRPM7 has been suggested to have a central role in cellular Mg 2+ homeostasis (Schmitz et al, 2003), in central nervous system ischemic injury (Aarts et al, 2003), in skeletogenesis in zebrafish (Elizondo et al, 2005), in the defecation rhythm in Caenorhabditis elegans (Vriens et al, 2004), in cholinergic vesicle fusion with the plasma membrane (Brauchi et al, 2008), in phosphoinositide-3-kinase signaling in lymphocytes (Sahni et al, 2008), in cell death in gastric cancer (Kim et al, 2008), in osteoblast proliferation (Abed et al, 2009) and in breast cancer cell proliferation (Guilbert et al, 2009). But, until now, the effect of the 5-LOX inhibitors, NDGA, AA861 and MK886 on these TRPM7 several physiological functions have not yet been investigated.…”

Magnesium in the Central Nervous System

“…The molecular mechanisms involved have not been completely disclosed, but it is known that Na--dependent Mg extrusion is impaired in tumour cells and contributes to elevate intracellular Mg . In addition, TRPM7 is overexpressed in breast tumours and in neoplastic cultured cells (Guilbert et al, 2009), and this feature may well account for the avidity of cancer cells for extracellular Mg. Also nuclear Mg content is higher in neoplastic than in normal cells (Lukacs et al, 1996). Considering that Mg acts a second messenger and activates a vast array of enzymes, it is noteworthy that not only does intracellular Mg increase, but it is also differently distributed in transformed vs normal cells.…”