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

Saisai Wang; Yuanyuan Yao; Xiao Wang; Gang Zheng; Wei Ouyang; Wenbin Chen

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

Am J Cancer Res. 2019 Oct 1;9(10):2140-2155. eCollection 2019.

Authors

Saisai Wang¹, Yuanyuan Yao¹, Xiao Wang¹, Gang Zheng², Wei Ouyang³, Wenbin Chen¹

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
PMCID: PMC6834473

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.