ReferenceID 3861

Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice

Hepatology

Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element

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Reference Id
3861
Evidence Id
20451
Core Evidence Id
20451
Source Reference Id
1010
Herb2 Reference Id
HBREF001729
Subject Paper Key
HBIN018374_28027595
Pubmed Id
28027595
Doi
10.1002/hep.29018
Paper Title
Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice
Paper Abstract
Obesity is a critical risk factor for hepatocellular carcinoma (HCC). However, it remains unknown whether inhibition of de novo lipid biosynthesis can suppress HCC. In this study, we blocked the sterol regulatory element-binding protein (SREBP) pathway, one of the key determinants of lipid homeostasis, by ablating 78-kDa cell-surface glycoprotein or SREBP cleavage-activating protein in hepatocytes, as well as by administering a chemical compound called betulin. We found that either genetically or pharmacologically inhibiting the SREBP pathway dramatically reduced diethylnitrosamine-induced HCC progression by down-regulating tumor-promoting cytokines, including interleukin (IL)-6, tumor necrosis factor alpha, and IL-1β.CONCLUSION: Inhibition of de novo lipid biosynthesis by suppressing the SREBP pathway prevents HCC. This study identifies a previously underappreciated role of the SREBP pathway in HCC and suggests a novel metabolic strategy to control liver cancer. (Hepatology 2017;65:1936-1947).
Journal
Hepatology
Publish Year
2017
Experiment Subject
hepatocytes
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Inhibition of the sterol regulatory element-binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice
Bilingual Status
semi_complete