title: Hepatic stellate cell promoted hepatoma cell invasion via the HGF/c-Met signaling pathway regulated by p53.
abstract: The biological behaviors of hepatocellular carcinoma (HCC) are complex mainly due to heterogeneity of progressive genetic and epigenetic mutations as well as tumor environment. Hepatocyte growth factor (HGF)/c-Met signaling pathway is regarded to be a prototypical example for stromal-epithelial interactions during developmental morphogenesis, wound healing, organ regeneration and cancer progression. And p53 plays as an important regulator of Met-dependent cell motility and invasion. Present study showed that 2 HCC cell lines, Hep3B and HepG2, displayed different invasive capacity when treated with HGF which was secreted by hepatic stellate cells (HSCs). We found that HGF promoted Hep3B cells invasion and migration as well as epithelial-mesenchymal transition (EMT) occurrence because Hep3B was p53 deficient, which leaded to the c-Met over-expression. Then we found that HGF/c-Met promoted Hep3B cells invasion and migration by upregulating Snail expression. In conclusion, HGF/c-Met signaling is enhanced by loss of p53 expression, resulting in increased ability of invasion and migration by upregulating the expression of Snail.
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Jing
authors.affiliation: c Oncology Department , Ji'an Hospital, Shanghai East Hospital, Tongji University School of Medicine , Shanghai , China.
authors.forename: Guo-feng
authors.initials: GF
authors.lastname: Yu
authors.affiliation: d Pathology Department , Funing Hospital of Traditional Chinese Medicine , Qinghuangdao , Hebei Province , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Zhi-peng
authors.initials: ZP
authors.lastname: Han
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.affiliation: e Ultrasonography Department , The First Affiliated Hospital of Soochow University , Jiangsu , China.
authors.forename: Qing-Min
authors.initials: QM
authors.lastname: Fan
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Qiu-Dong
authors.initials: QD
authors.lastname: Zhao
authors.affiliation: b Department of Comprehensive Treatment , Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000071250:Snail Family Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: EMT; HGF/c-Met; HSCs; hepatocellular carcinoma; invasion and migration; p53