AIM To investigate the role of suppressor of cytokine signaling 1(SOCS1)in regulating MET-mediated invasive potential of hepatocellular carcinoma(HCC)cells.METHODSStable 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 agar.Following intravenous and intrasplenic inoculation into NOD.scid.gamma mice,the ability of Hepa cells to form othotopic tumors was evaluated.Following HGF stimulation of Hepa and Hep3B cells,expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR T-PCR.RESULTS SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through matrigel.In the 3-D invasion assay,HGF stimulation induced invasion of HCC cells across type-Ⅰcollagen matrix,and SOCS1expression significantly reduced the depth of invasion.SOCS1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid agar.Following intravenous inoculation,control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller nodules.Tumors formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein expression.HGF stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1,SNAI1and ZEB1.Comparable results were obtained with Hep3B cells.SOCS1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 transcripts.CONCLUSION Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated migration,invasion and metastatic growth of HCC. AIM To investigate the role of suppressor of cytokine signaling 1 (SOCS1) in regulating MET-mediated invasive potential of hepatocellular carcinoma (HCC) cells. METHODSStable derivatives of mouse (Hepa 1-6) and human (hep3B, Hep G2) HCC cell lines expressing SOCS1or control vectors were evaluated for their ability to migrate toward 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 anchorage independent proliferation in semisolid agar .Following intravenous and intrasplenic inoculation into NOD. Scid.gamma mice, the ability of Hepa cells to form othotopic tumors was evaluated. Flowing HGF stimulation of Hepa and Hep3B cells, expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR T-PCR .RESULTS SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through matrigel. the 3-D invasion assay, HGF stimulation induced invasion of HCC cells across type-I colagen matrix, and SOCS1 expression significantly reduced the depth of invasion. SOCS1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid agar. Popular intravenous inoculation, control Hepa cell formed large tumor nodules that obliterated the liver while the SOCS1-expressing Hepatocytes formed significantly smaller nodules. Tumors formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein expression. HGF stimulated Hepa cells expressing SOCS1 showed Increased expression of E-cadherin and decreased expression of EGR1, SNAI1 and ZEB1.Comparable results were with Hep3B cells. SOCS1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 transcript. CONCLUSION Our profiles indicate that loss of SOCS1-dependent control over epithelial -to-mesenchymal transition may contribute to MET-mediated mmigration, invasion and metastatic growth of HCC.