title: Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through ERK signaling pathway.
abstract: Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3 contributes to the progress of HCC is largely unclear. The present study investigated the association between GPC3 expression and HCC clinicopathological characteristics, and particularly focused on the role and underlying mechanisms of GPC3 in HCC epithelial-mesenchymal transition (EMT). Remarkably elevated expression of GPC3 was demonstrated in HCC tumor tissues compared with paired non-tumor tissues in 45 patients with HCC by quantitative real-time PCR, immunohistochemistry, and western blotting, respectively. Furthermore, the tissue expression of GPC3 was increased during HCC progression from Barcelona Clinic Liver Cancer stage A or B to stage C. The enhanced levels of GPC3 in HCC tumor tissues were tightly correlated to the expression of the EMT-associated proteins and tumor vascular invasion. Patients with GPC3-high expression in tumor tissues displayed significantly shorter survival time than those with GPC3-low expression (P=0.001). Consistent with the findings in patients, HepG2 cells, which expressed high levels of GPC3, showed stronger capacity of migration and significant EMT-like changes when compared to those HCC cells with low levels of GPC3, e.g., Hep3B and Huh7 in scratch, Transwell assays and western blotting. Furthermore, administration with exogenous GPC3 in HCC cells activated extracellular signal-regulated kinase (ERK) and significantly enhanced cell migration and invasion. The behavior was significantly inhibited by the ERK inhibitor PD98059. Together, our studies show that GPC3 contributes to HCC progression and metastasis through impacting EMT of cancer cells, and the effects of GPC3 are associated with ERK activation.
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Yongle
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Hepatology, University of Heidelberg, University Medical Center Mannheim, D-68167 Mannheim, Germany.
authors.forename: Honglei
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Molecular Hepatology, University of Heidelberg, University Medical Center Mannheim, D-68167 Mannheim, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Department of Gastroenterology and Hepatology, Beijing You'an Hospital Affiliated with Capital Medical University, Fengtai District, Beijing 100069, P.R. China.
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D053673:Glypicans / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans