Liver-specific SIRT1 knockout-induced hyperglycemia promotes spontaneous lung adenocarcinomas through HSF1-MDM2 - PubMed
4 hours ago
- #lung adenocarcinoma
- #SIRT1 knockout
- #hyperglycemia
- Epidemiological studies link metabolic diseases with higher cancer risk.
- Liver-specific SIRT1 knockout mice develop hyperglycemia early and later show increased susceptibility to lung adenocarcinomas.
- Hyperglycemia in these mice leads to elevated MDM2 oncoprotein levels, downregulating p21 and GADD45 genes.
- MDM2 disruption impairs cell cycle checkpoints, increases proliferation, and promotes genomic instability in lung epithelia.
- HSF1 transcription factor regulates MDM2; high glucose reduces nuclear HSF1, and its knockdown boosts MDM2 and cell proliferation.
- Human lung adenocarcinomas show high MDM2 levels, correlating with survival rates, suggesting hyperglycemia may be a lung cancer risk factor.