title: Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma.
abstract: Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and that this expression was positively correlated with that of VEGF-A. Additionally, L-FABP significantly promoted tumor growth and metastasis in a xenograft mouse model. We also assessed the mechanisms of L-FABP activity in tumorigenesis; L-FABP was found to associate with VEGFR2 on membrane rafts and subsequently activate the Akt/mTOR/P70S6K/4EBP1 and Src/FAK/cdc42 pathways, which resulted in up-regulation of VEGF-A accompanied by an increase in both angiogenic potential and migration activity. Our results thus suggest that L-FABP could be a potential target for HCC chemotherapy.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Ku
authors.affiliation: Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan.
authors.forename: Hsuan-Yuan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan.
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Lu
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan.|Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan.
authors.forename: Jung-Yaw
authors.initials: JY
authors.lastname: Lin
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020764:cdc42 GTP-Binding Protein
keywords: angiogenesis; hepatocellular carcinoma; liver fatty acid-binding protein; vascular endothelial growth factor