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.
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Yijie
Y
Chen
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Yang
Y
Yu
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Shuya
S
Sun
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Zhaotong
Z
Wang
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; National and Local Joint Engineering Laboratory of Druggabilitiy Assessment and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Peiqing
P
Liu
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
Shenglan
S
Liu
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: lssjjm@mail.sysu.edu.cn.
Jianmin
J
Jiang
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D000069261:Podosomes / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D050053:TRPM Cation Channels; D010768:Phosphoserine; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D002154:Calpain; D020778:Matrix Metalloproteinase 2; D018995:Myosin Heavy Chains; D001920:Bradykinin; D002118:Calcium
Bradykinin; Invasion; MMP2; Migration; TRPM7