PP1A Modulates the Efficacy of Lenvatinib Plus ICIs Therapy by Inhibiting Ferroptosis in Hepatocellular Carcinoma.

ABSTRACT: Advanced hepatocellular carcinoma (HCC) is characterized by poor prognosis, primarily due to limited therapeutic options and resistance to treatment. Although the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has shown promising potential, the underlying mechanisms remain inadequately understood. Here, serine/threonine-specific protein phosphatase (PP1A) is upregulated in Lenvatinib-resistant HCC cells and correlates with poor prognosis. Functional experiments revealed that PP1A promotes HCC progression both in vitro and in vivo. Transcriptomic analysis and ferroptosis metabolite profiling (e.g., ROS, Fe²⁺, lipid-ROS, and GSH) demonstrated that PP1A inhibits Lenvatinib-induced ferroptosis by dephosphorylating Keap1 at site 104. This dis

SUBMITTER: Zhou J 

PROVIDER: S-EPMC12279197 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature