肝脏脂肪酸结合蛋白（L-FABP）促进肝细胞癌中的细胞血管生成和迁移。
Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma.
作者信息
Ku Chung-Yu, Liu Yu-Huei, Lin Hsuan-Yuan, Lu Shao-Chun, Lin Jung-Yaw
机构信息
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan.
Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan.
出版信息
Oncotarget. 2016 Apr 5;7(14):18229-46. doi: 10.18632/oncotarget.7571.
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.
肝脏脂肪酸结合蛋白（L-FABP）在肝细胞中含量丰富，已知其参与脂质代谢。已有报道称L-FABP在多种癌症中过表达；然而，其在肝细胞癌（HCC）中的作用仍不清楚。在本研究中，我们调查了90例HCC患者中L-FABP及其与血管内皮生长因子（VEGFs）的关联。我们发现L-FABP在其HCC组织中高表达，且这种表达与VEGF-A的表达呈正相关。此外，在异种移植小鼠模型中，L-FABP显著促进肿瘤生长和转移。我们还评估了L-FABP在肿瘤发生中的作用机制；发现L-FABP与膜筏上的VEGFR2相关联，随后激活Akt/mTOR/P70S6K/4EBP1和Src/FAK/cdc42信号通路，这导致VEGF-A上调，同时血管生成潜能和迁移活性增加。因此，我们的结果表明L-FABP可能是HCC化疗的潜在靶点。
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