Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation.

ABSTRACT: Insufficient microwave ablation (IMWA) is linked to aggressive hepatocellular carcinoma (HCC) progression. An increase in lactate levels after sublethal heat stress (HS) has been confirmed in HCC. However, the role of lactate-related histone lactylation in the progression of HCC caused by sublethal HS remains unclear. Here, we found that the metastatic potential of HCC increased in a lactate-dependent manner after IMWA. Moreover, sublethal HS triggered an increase in H3K18la modification, as validated in a cell-derived xenograft mouse model and human HCC samples. By performing an integrated analysis of proteomic and transcriptomic profiles, we revealed that HCC cells exhibited increased intracellular iron ion homeostasis and developed resistance to platinum-based drugs after exposure to su

SUBMITTER: Huang J 

PROVIDER: S-EPMC11876915 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature