25-HC promotes hepatocellular carcinoma metastasis through up-regulation of TLR4 dependent FABP4

  • Am J Cancer Res. 2019 Oct 1;9(10):2140-2155.
Saisai Wang  1 ,  Yuanyuan Yao  1 ,  Xiao Wang  1 ,  Gang Zheng  2 ,  Wei Ouyang  3 ,  Wenbin Chen  1
Affiliations
  • 1. Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, P. R. China.
  • 2. Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, P. R. China.
  • 3. Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, P. R. China.
PMID: 31720079
Abstract

Metabolic syndrome is a significant risk factor for the development of hepatocellular carcinoma (HCC). 25-HC (25-hydroxycholesterol) synthesized from Cholesterol plays an important role in lipid metabolism. However, the functions and mechanism of 25-HC in HCC remain largely unknown. In this study, we demonstrated that 25-HC promoted HCC cells migration and intrahepatic and extrahepatic metastasis while did not affect the cells proliferation and Apoptosis. Mechanistically, the promotive effect of 25-HC was through up-regulation of Toll-like Receptor 4 (TLR4) dependent fatty acid binding protein 4 (FABP4). Inhibition of FABP4 hindered 25-HC-induced cells migration and metastasis. Moreover, up-regulation of FABP4 was observed in HCC tissues from database analysis. In summary, our study reveals the effects and mechanism of 25-HC/TLR4/FABP4 axis in promoting HCC metastasis, which provides novel avenue for therapeutic intervention against HCC progression.

Keywords
25-hydroxycholesterol; Toll-like receptor 4; fatty acid binding protein 4; hepatocellular carcinoma; metastasis.
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