ENO1 lactylation drives bevacizumab resistance through metabolic reprogramming and angiogenesis in ovarian cancer - PubMed
3 hours ago
- #Ovarian Cancer
- #Bevacizumab Resistance
- #Metabolic Reprogramming
- ENO1 lactylation at lysine 71 (K71), mediated by AARS1, is identified as a key driver of bevacizumab resistance in ovarian cancer.
- Elevated pan-lactylation in bevacizumab-resistant tissues correlates with enhanced angiogenesis and poor prognosis.
- ENO1 lactylation increases lactate synthesis and promotes histone lactylation marks (H3K9la, H3K14la), upregulating transcription of the angiogenic factor ESM1.
- ESM1 stabilizes YY1 in endothelial cells by inhibiting Smurf2-mediated ubiquitination, enhancing YY1-dependent EP300 recruitment and H3K27 acetylation at the BCL2A1 promoter.
- This cascade promotes endothelial cell survival and angiogenesis, establishing a positive feedback loop that fosters bevacizumab resistance, highlighting ENO1 lactylation as a potential therapeutic target.