Open AccessThe regulatory role of heparin on c‐Met signaling in hepatocellular carcinoma cells
Author(s) -
İşcan Evin,
Güneş Aysim,
Korhan Peyda,
Yılmaz Yeliz,
Erdal Esra,
Atabey Neşe
Publication year - 2017
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-016-0368-0
Subject(s) - hepatocyte growth factor , heparin , cancer research , protein kinase b , medicine , matrix metalloproteinase , carcinogenesis , signal transduction , c met , hepatocellular carcinoma , motility , pharmacology , cancer , biology , microbiology and biotechnology , receptor
The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)‐induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c‐Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c‐Met receptor dimerization and activated c‐Met signaling in an HGF independent manner. Heparin‐induced c‐Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c‐Met signaling reversed heparin‐induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c‐Met signaling in HCC.