Stiffness-activated hepatic stellate cells boost HCC migration via TGM2/ITGB1-mediated matrix remodeling and mitochondrial transfer.

ABSTRACT:

Background & aims

High liver stiffness correlates with poor outcomes in hepatocellular carcinoma (HCC). Prior studies focused on neoplastic cells rather than the tumor microenvironment. This study investigated how the tumor microenvironment, particularly mechanosignaling in hepatic stellate cells (HSCs), drives HCC progression.

Methods

The study examined the roles of transglutaminase 2 (TGM2) and integrin β1 (ITGB1) in HSCs under mechanical stress through proteomics, cell contraction assays, and protein interactions. It also analyzed gene expression data from 178 patients with HCC and cirrhosis to assess the impact of TGM2 and ITGB1 on overall survival (OS). Mitochondrial transfer and cell migration were observed using confocal microscopy, and the effect of TGM2/ITGB1 on ext

SUBMITTER: Wang M 

PROVIDER: S-EPMC12464549 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature