Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147⁺ extracellular vesicles promotes sorafenib resistance of hepatocellular carcinoma.

ABSTRACT: Background: Transarterial chemoembolization (TACE) combined with sorafenib is a common therapeutic strategy for hepatocellular carcinoma (HCC). However, sorafenib resistance (SFR) remains a major clinical obstacle. Evidence suggest that TACE reshapes the tumor microenvironment (TME), creating an external high-glucose (HG) and internal low-glucose (LG) niche. In this context, hyperglycemia-driven lysophosphatidic acid (LPA) production accelerates HCC progression. Moreover, intercellular communication via extracellular vesicles (EVs) has been linked to drug resistance. Despite these insights, the SFR mechanism by which HG-induced LPA regulates EV uptake and signaling is unclear. Methods: ELISA, immunohistochemistry, Western blot, CCK-8, Annexin V-7AAD, bioinformatics, and hyper

SUBMITTER: Qian L 

PROVIDER: S-EPMC12681849 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature