Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer

Abstract

CaAmong ion channels, the transient receptor potential (TRP) melastatin 6 and 7 channel is similarly permeable to both of the dominant divalent cations Ca 2+ and Mg 2+ .(4) TRP channels were first cloned from the Drosophila species (TRP and transient receptor potential-like protein) and constitute a superfamily of proteins that encode a diverse group of Ca 2+ -permeable nonselective cation channels.(5) The TRP family is divided into three subfamilies: classic, vanilloid (TRPV), and melastatin type (TRPM).(5) The eight TRPM family members differ significantly from other TRP channels in terms of domain structure, cation selectivity, and activation mechanisms.(5) By mediating cation entry as well as membrane depolarization, activation of the TRPM subfamily of ion channels has a profound influence on various physiologic and pathologic processes. (6,7) TRPM7 is endogenously expressed in a wide variety of tissues including brain and hematopoietic tissues (8) as well as kidney and heart tissues.(9-11) The TRPM7 cation channel supports multiple cellular and physiological functions, including cellular Mg 2+ homeostasis, (12,13) cell viability and growth, (13)(14)(15)(16) anoxic neuronal cell death, (17) synaptic transmission, (18) cell adhesion, (19,20) and intestinal pacemaking.(21) Recently, Wykes et al. (22) suggested that TRPM7 channels are critical for human mast cell survival, and Jiang et al. (23) suggested that activation of TRPM7 channels is critical for the growth and proliferation of human head and neck carcinoma cells. Also Abed et al. (24) proposed the importance of TRPM7 in human osteoblast-like cell proliferation. However, the presence and potential function of TRPM7 channels in human gastric cancer cells are unknown.In this study, we examined the presence and potential role of TRPM7 channels in the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell line. Our data suggest that TRPM7 channels have an important role in the survival of these tumor cells. Materials and MethodsCells. Five human gastric adenocarcinoma cell lines (AGS, MKN-1, MKN-45, SNU-1, and SNU-484) were used. Among them, we used mainly AGS cell line, the most common human gastric adenocarcinoma cell line. All cell lines were established at

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

“…Mazzone et al (2011) suggested that Changes in Ca 2+ -activated Cl -conductances expression in ICCs may directly contribute to human diabetic gastroparesis. However, Kim et al (2008) suggested TRPM7 has an important role in gastric cancer cell death. The exact functions of TRPM7 and Ca 2+ -activated Cl -conductances in GI tract need to be investigated in future.…”

“…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.…”

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

“…Kim et al [9] reported that human gastric adenocarcinoma cells express TRPM7 channel and that this channel is essential for cell survival. In addition, they suggested that this channel be viewed as a potential target for the pharmacological treatment of gastric cancer.…”

“…In previous studies, we found that human gastric adenocarcinoma (AGS) cells express the transient receptor potential melastatin 7 (TRPM7) channel, which is known to be essential for cell survival and has been suggested as a pharmacological target for the treatment of gastric cancer [9]. Therefore, we investigated whether waixenicin A influences AGS cell 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].…”