Lactylation‐Driven IGF2BP3‐Mediated Serine Metabolism Reprogramming and RNA m6A—Modification Promotes Lenvatinib Resistance in HCC
Zhengzhou University · Henan Provincial People's Hospital · +6 more institutions
Abstract
Acquired resistance remains a bottleneck for molecular-targeted therapy in advanced hepatocellular carcinoma (HCC). Metabolic adaptation and epigenetic remodeling are recognized as hallmarks of cancer that may contribute to acquired resistance. In various lenvatinib-resistant models, increased glycolysis leads to lactate accumulation and lysine lactylation of IGF2BP3. This lactylation is crucial for capturing PCK2 and NRF2 mRNAs, thereby enhancing their expression. This process reprograms serine metabolism and strengthens the antioxidant defense system. Additionally, altered serine metabolism increases the availability of methylated substrates, such as S-adenosylmethionine (SAM), for N6-methyladenosine (m6A)…
Citation impact
- FWCI
- 22.58
- Percentile
- 100%
- References
- 71
Authors
11- YLYuanxiang Lu
Zhengzhou University, Henan Provincial People's Hospital, Tongji Hospital, Huazhong University of Science and Technology
- JZJinghan Zhu
Tongji Hospital, Huazhong University of Science and Technology
- YZYuxin Zhang
Tongji Hospital, Huazhong University of Science and Technology
- WLWentao Li
Zhengzhou University, Henan Provincial People's Hospital
- YXYixiao Xiong
Tongji Hospital, Huazhong University of Science and Technology
Topics & keywords
- Lenvatinib
- Reprogramming
- Cancer research
- Serine
- Epigenetics
- Biology
- Chemistry
- Cell biology