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

Bradykinin promotes migration and invasion of hepatocellular carcinoma cells through TRPM7 and MMP2
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DOI:
10.1016/j.yexcr.2016.09.022
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发表时间:
2016-11-15
影响因子:
3.7
通讯作者:
Jiang, Jianmin
Jiang, Jianmin
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Yijie;Yu, Yang;Jiang, Jianmin

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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 Cat(2+) via TRPM7 was necessary for elevating the activity of m-calpain and p-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.