Cancer-associated fibroblasts derived fibronectin extra domain A promotes sorafenib resistance in hepatocellular carcinoma cells by activating SHMT1.

ABSTRACT: Resistance to sorafenib, an effective first-line treatment for advanced hepatocellular carcinoma (HCC), greatly compromised the prognosis of patients. The extracellular matrix is one of the most abundant components of the tumor microenvironment. Beyond acting as a physical barrier, it remains unclear whether cell interactions and signal transduction mediated by the extracellular matrix contribute to sorafenib resistance. With the analysis of primary HCC organoid RNA-seq data combined with in vivo and in vitro experiments validation, we discovered that fibronectin extra domain A (FN-EDA) derived from cancer-associated fibroblasts played a critical role in sorafenib resistance. Mechanistically, FN-EDA stimulates the up-regulation of the key one-carbon metabolism enzyme SHMT1 in

SUBMITTER: Dong Y 

PROVIDER: S-EPMC11402957 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature