title: Tetraspanin 8 mediates AEG-1-induced invasion and metastasis in hepatocellular carcinoma cells.
abstract: Astrocyte-elevated gene-1 (AEG-1) positively regulates tumor progression and metastasis. Here, we document that AEG-1 upregulates transcription of the membrane protein tetraspanin 8 (TSPAN8). Knocking down TSPAN8 in AEG-1-overexpressing human hepatocellular carcinoma (HCC) cells markedly inhibited invasion and migration without affecting proliferation. TSPAN8 knockdown profoundly abrogated AEG-1-induced primary tumor and intrahepatic metastasis in an orthopic xenograft model in athymic nude mice. Coculture of TSPAN8 knockdown cells with human umbilical vein endothelial cells (HUVEC) markedly inhibited HUVEC tube formation indicating that inhibition of angiogenesis might cause reduction in primary tumor size. TSPAN8 inhibition might be a potential therapeutic strategy for metastatic HCC.
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Maaged A
authors.identifier: 0000-0002-0211-2837
authors.initials: MA
authors.lastname: Akiel
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Prasanna K
authors.initials: PK
authors.lastname: Santhekadur
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Mendoza
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Siddiq
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.|VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.|VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.affiliation: Departments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.|VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.|VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins; D059470:Tetraspanins / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C065609:TSPAN8 protein, human; D059470:Tetraspanins
keywords: angiogenesis; astrocyte-elevated gene-1; invasion; metastasis; tetraspanin 8