MLKL in liver parenchymal cells promotes liver cancer in murine metabolic dysfunction-associated steatotic liver disease - PubMed
3 days ago
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- #HCC
- #MASLD
- MLKL in liver parenchymal cells (LPCs) promotes hepatocellular carcinoma (HCC) in metabolic dysfunction-associated steatotic liver disease (MASLD).
- Mice lacking MLKL in LPCs (MlklLPC-KO) showed reduced liver tumor incidence compared to controls (Mlklfl/fl) under a high-fat high-sugar diet (HFHSD).
- No detectable hepatic necroptosis or phosphorylated MLKL was observed in control mice, despite similar steatosis and fibrosis progression.
- MLKL absence in LPCs reduced early metabolic stress, oxidative stress, and DNA damage, delaying systemic and hepatic inflammation.
- MLKL may contribute to HCC initiation via non-canonical mitochondrial roles, suggesting therapeutic potential for MLKL inhibition in MASH-related HCC.