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Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1

World Journal of Gastroenterology 2017年第36期23卷 6639-6649页

作者： Yirui Gui Md Gulam Musawwir Khan Diwakar Bobbala Claire Dubois Sheela Ramanathan caroline saucier Subburaj Ilangumaran Department of Pediatrics Immunology DivisionFaculty of Medicine and Health SciencesUniversity of Sherbrooke Department of Anatomy and Cell Biology Faculty of Medicine and Health SciencesUniversitéde Sherbrooke

AIM To investigate the role of suppressor of cytokine signaling 1(SOCS1)in regulating MET-mediated invasive potential of hepatocellular carcinoma(HCC)*** derivatives of mouse(Hepa1-6)and human(hep3B,Hep G2)HCC cell lines expressing SOCS1or control vector were evaluated for their ability to migrate towards hepatocyte growth factor(HGF)in the transwell migration assay,invade extracellular matrix in response to HGF stimulation in a 3-D invasion assay by confocal microscopy,and to undergo anchorageindependent proliferation in semisolid *** intravenous and intrasplenic inoculation into *** mice,the ability of Hepa cells to form othotopic tumors was *** HGF stimulation of Hepa and Hep3B cells,expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR *** SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through *** the 3-D invasion assay,HGF stimulation induced invasion of HCC cells across type-Ⅰcollagen matrix,and SOCS1expression significantly reduced the depth of ***1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid *** intravenous inoculation,control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller *** formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein *** stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1,SNAI1and *** results were obtained with Hep3B ***1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 *** Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated m

关键词： Migration Invasion MET Hepatocellular carcinoma Suppressor of cytokine signaling 1

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