Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma
Journal
Oncotarget
Journal Volume
7
Journal Issue
14
Pages
18229-18246
Date Issued
2016
Author(s)
Ku C.-Y.
Liu Y.-H.
Lin H.-Y.
SHAO-CHUN LU
Lin J.-Y.
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.
Subjects
Angiogenesis; Hepatocellular carcinoma; Liver fatty acid-binding protein; Vascular endothelial growth factor
SDGs
Other Subjects
fatty acid binding protein; focal adhesion kinase; initiation factor 4E binding protein 1; mammalian target of rapamycin; protein Cdc42; protein kinase B; protein kinase p60; S6 kinase; vasculotropin A; vasculotropin receptor 2; FABP1 protein, human; fatty acid binding protein; focal adhesion kinase 1; KDR protein, human; MTOR protein, human; protein Cdc42; protein kinase B; PTK2 protein, human; S6 kinase; target of rapamycin kinase; vasculotropin A; vasculotropin receptor 2; VEGFA protein, human; adult; angiogenesis; animal experiment; animal model; Article; cell migration; controlled study; correlational study; female; human; human cell; human tissue; in vivo study; lipid metabolism; liver carcinogenesis; liver cell carcinoma; major clinical study; male; metastasis; middle aged; mouse; nonhuman; protein expression; protein targeting; signal transduction; tumor growth; tumor promotion; tumor xenograft; upregulation; animal; cancer transplantation; cell motion; cell transformation; Hep-G2 cell line; liver; liver cell; liver cell carcinoma; liver tumor; metabolism; neovascularization (pathology); nonobese diabetic mouse; pathology; physiology; SCID mouse; tumor cell line; umbilical vein endothelial cell; vascularization; xenograft; Animals; Carcinoma, Hepatocellular; cdc42 GTP-Binding Protein; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; Fatty Acid-Binding Proteins; Female; Focal Adhesion Kinase 1; Hep G2 Cells; Hepatocytes; Human Umbilical Vein Endothelial Cells; Humans; Liver; Liver Neoplasms; Male; Mice; Mice, Inbred NOD; Mice, SCID; Middle Aged; Neoplasm Transplantation; Neovascularization, Pathologic; Proto-Oncogene Proteins c-akt; Ribosomal Protein S6 Kinases, 70-kDa; TOR Serine-Threonine Kinases; Transplantation, Heterologous; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
Publisher
Impact Journals LLC
Type
journal article