TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca 2+ influx

Abstract

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.