Bradykinin promotes migration and invasion of hepatocellular carcinoma cells through TRPM7 and MMP2

Tumor metastasis is the main reason of death for hepatocellular carcinoma (HCC) patients. Cell migration and invasion are two prerequisites for tumor metastasis, in which TRPM7 and MMPs play an important role. In our study, we found that bradykinin (BK) could upregulate the expression of TRPM7 and dynamically regulate the phosphorylation of non-muscle myosin IIA heavy chain (NMHC-IIA) Ser-1943 in HepG2 cells. The influx of Ca2+ via TRPM7 was necessary for elevating the activity of m-calpain and μ-calpain. Additionally, we observed that BK stimulated HepG2 cells to secrete more MMP2 but not MMP9. Src was critical in the process of MMP2 secretion and invadopodia formation. The heat map showed that BDKRB2, TRPM7 and MMP2 had higher overexpression proportions in 25 HCC cell lines. Some clinical specimens of HCC also indicated that BDKRB2 and MMP2 were overexpressed. In conclusion, BK promoted migration and invasion of HCC cells through TRPM7 and MMP2. •Bradykinin promoted migration and invasion of HepG2 cells through TRPM7 and MMP2.•The effect of Bradykinin on NMHC-IIA Ser-1943 was similar to EGF's.•Ser-1943 could be an overlooked phosphorylation site on NMHC-IIA for TRPM7.•Both NM-IIA and calpains were important for migrating cancer cells.•Src regulated the invadopodia formation and MMP2 secretion of HepG2 cells.