Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma

Chung-Yu Ku; Yu-Huei Liu; Hsuan-Yuan Lin; Shao-Chun Lu; Jung-Yaw Lin

doi:10.18632/oncotarget.7571

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Research Papers:

Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma

Chung-Yu Ku, Yu-Huei Liu, Hsuan-Yuan Lin, Shao-Chun Lu _ and Jung-Yaw Lin

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Oncotarget. 2016; 7:18229-18246. https://doi.org/10.18632/oncotarget.7571

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Abstract

Chung-Yu Ku1, Yu-Huei Liu2, Hsuan-Yuan Lin3, Shao-Chun Lu1, Jung-Yaw Lin1,3

1Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City, Taiwan

2Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan

3Department of Life Science, National Taiwan Normal University, Taipei City, Taiwan

Correspondence to:

Shao-Chun Lu, e-mail: [email protected]

Jung-Yaw Lin, e-mail: [email protected]

Keywords: angiogenesis, hepatocellular carcinoma, liver fatty acid-binding protein, vascular endothelial growth factor

Received: July 22, 2015 Accepted: January 29, 2016 Published: February 22, 2016

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.

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Research Papers:

Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma

Abstract