AARS1‐mediated AKR1B10 lactylation stabilizes an aerobic glycolysis‐positive feedback loop to drive lenvatinib resistance in hepatocellular carcinoma
AKR1B10 confers lenvatinib resistance by enhancing aerobic glycolysis in HCC cells. AKR1B10 undergoes AARS1-mediated lactylation at K173, stabilizing it by antagonizing ubiquitin-proteasomal degradation. AKR1B10 promotes LDHA Y10 phosphorylation, boosting lactate production, which drives H3K18la-mediated transcriptional upregulation of LDHA, creating a feed-forward loop. Targeting AKR1B10 with epalrestat synergizes with lenvatinib to overcome resistance in preclinical models.
Authors
- Jingsheng Yuan (ORCID: https://orcid.org/0000-0002-2862-6553)
- Shitong Su (ORCID: https://orcid.org/0009-0008-8150-1654)
- Yuhan Ma
- Jiaqi Han
- Zijian Liu
- Tao Lv
- Nianyong Chen
- Ni Zeng
Institutions
- Sichuan University (CN)
- West China Second University Hospital of Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
- Sichuan Cancer Hospital (CN)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1002/ctm2.70561
- Citations
- 1
- Primary Topic
- Aldose Reductase and Taurine
- Type
- article
- Field-Weighted Citation Impact
- 1.15