TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2+) influx.
Ion channels are involved in various physiologic and pathologic processes, including the migration of tumor cells that is required for metastasis. To determine whether transient receptor potential melastatin 7 (TRPM7) Ca(2+) channels play an important role in the migration of tumor cells, we examined the potential function of TRPM7 channels in the migration of 5-8F and 6-10B human nasopharyngeal carcinoma cells. The migratory potential of 5-8F cells was significantly decreased by extracellular Ca(2+) chelator (EGTA), TRPM7 inhibitors (La(3+), 2-APB), or TRPM7 knockdown. Conversely, the addition of TRPM7 activator Bradykinin and overexpression of TRPM7 promoted the migration of 5-8F and 6-10B cells. Furthermore, the sustained Ca(2+) influx regulated by TRPM7 activated release of Ca(2+) stores via ryanodine receptors by a calcium-induced calcium release (CICR) mechanism. This study suggests, first, that Ca(2+) influx is required for the migration of human nasopharyngeal carcinoma 5-8F cells. Second, and more importantly, it identifies TRPM7 as a novel potential-regulator of the Ca(2+) influx that allows migration of 5-8F cells. TRPM7, therefore, might have potential as a prognostic indicator and as a therapeutic target in nasopharyngeal carcinoma.
Chen
Jian-Peng
JP
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
Luan
Yi
Y
You
Chang-Xuan
CX
Chen
Xiao-Hua
XH
Luo
Rong-Cheng
RC
Li
Rong
R
D001896:Boron Compounds / Q000737:chemistry / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004533:Egtazic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
D001896:Boron Compounds; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; D004533:Egtazic Acid; C109986:2-aminoethoxydiphenyl borate; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D001920:Bradykinin; D002118:Calcium