title: Overexpression of syntenin enhances hepatoma cell proliferation and invasion: potential roles in human hepatoma.
abstract: Hepatocellular carcinoma (HCC) ranks as the third leading cause of tumor-related mortality worldwide. Recently, syntenin was found to be upregulated in several tumors and to exert pivotal roles in the development of cancer. However, its function and the underlying mechanism in HCC remain to be defined. In the present study, the elevated expression levels of syntenin mRNA and protein were detected in four HCC cell lines. Overexpression of syntenin in hepatoma HCCLM3 cells enhanced cell proliferation. Furthermore, syntenin upregulation increased epidermal growth factor receptor (EGFR) expression, which accounted for syntenin‑induced cell proliferation as precondition with EGFR siRNA clearly attenuated cell proliferation in syntenin-transfected cells. At the same time, syntenin overexpression promoted cell invasion by MMP-2, as pretreatment with anti-MMP-2 antibody blocked syntenin-induced invading cell numbers. Additionally, syntenin upregulation induced the phosphorylation of p38 MAPK contributing to the increase in MMP-2 expression, as treatment with the specific inhibitor for p38 MAPK (SB203580) clearly abrogated MMP-2 expression induced by syntenin. Collectively, our results suggest that syntenin overexpression plays a critical role in promoting the proliferation and invasion of hepatoma cells. Therefore, the present study provides new insight into how syntenin accelerates the development and progression of hepatoma, and suggests that syntenin may be a promising therapeutic agent against hepatoma.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shi
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011725:Pyridines / Q000008:administration & dosage; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D053676:Syntenins; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D053676:Syntenins; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C093642:SB 203580