The following is the summary of  “HDLBP Promotes Hepatocellular Carcinoma Proliferation and Sorafenib Resistance by Suppressing Trim71-dependent RAF1 Degradation” published is the January 2023 issue of Cellular and Molecular Gastroenterology and Hepatology by Yuan, et al.

Attractive study areas include the role that aberrant metabolic targets play in the development of hepatocellular carcinoma (HCC) and the regulatory mechanisms that govern this process. However, few studies have established a function for high-density lipoprotein binding protein (HDLBP) in HCC progression, despite the fact that HDLBP is an essential transporter that protects cells from excessive cholesterol accumulation. HCC tissues and previously published data sets were analyzed for HDLBP expression. A number of functional tests were carried out to investigate the biological functions of HDLBP in vitro and in vivo.

HDLBP expression was shown to be considerably higher in HCC compared to noncancerous liver tissues in an integrative analysis. HCC growth and sorafenib resistance were markedly reduced by HDLBP knockdown or increased by HDLBP overexpression, respectively. Mass spectrometry screening then pinpointed RAF1 as an HDLBP downstream target. Specifically, MEKK1 constantly activated RAF1ser259- dependent MAPK signaling when RAF1 was maintained by HDLBP. 

However, HDLBP prevented RAF1 degradation via the ubiquitin-proteasome pathway by interacting with RAF1 and interfering with the TRIM71 E3 ligase. The current research establishes HDLBP as a critical mediator that promotes HCC progression and sorafenib resistance by stabilizing and maintaining the activity of the RAF1 protein. As a result, HDLBP may serve as a biomarker and a future therapeutic target for hepatocellular carcinoma.