Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis.

ABSTRACT: Hepatocellular carcinoma (HCC) is the 3^rd most deadly malignancy. Activated hepatic stellate cells (aHSC) give rise to cancer-associated fibroblasts in HCC and are considered a potential therapeutic target. Here we report that selective ablation of stearoyl CoA desaturase-2 (Scd2) in aHSC globally suppresses nuclear CTNNB1 and YAP1 in tumors and tumor microenvironment and prevents liver tumorigenesis in male mice. Tumor suppression is associated with reduced leukotriene B4 receptor 2 (LTB4R2) and its high affinity oxylipin ligand, 12-hydroxyheptadecatrienoic acid (12-HHTrE). Genetic or pharmacological inhibition of LTB4R2 recapitulates CTNNB1 and YAP1 inactivation and tumor suppression in culture and in vivo. Single cell RNA sequencing identifies a subset of tumor-associated aHS

SUBMITTER: Sinha S 

PROVIDER: S-EPMC10167314 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature