ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
N6-Methyladenosine modification activates the serine synthesis pathway to mediate therapeutic resistance in liver cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global research status and frontiers on ferroptosis in hepatocellular carcinoma: a comprehensive bibliometric and visualized analysis.Frontiers in immunology · 2025Pooled it
- Article
- Review
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
- Targeting IGF2BP3 in Cancer: From Molecular Structure and Biology to Early Drug Discovery.International journal of molecular sciences · 2026Review
- Regulation of PSAT1 and PHGDH by m6A in endocrine-resistant breast cancer cells.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- IGF2BP2-driven serine metabolism promotes the progression of thyroid carcinoma via mJournal of translational medicine · 2026Article
- Effects and molecular mechanism of inhibiting p53 signaling pathway by NSUN4 on the resistance to BCL-2 inhibitor for diffuse large B-cell lymphoma.Clinical and experimental medicine · 2026Article
- METTL3-mediated N6-methyladenosine modification ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- NRAV promotes HCC stemness via the m6A-regulated let-7c-5p/LIN28B axis.Cancer gene therapy · 2026Article
- The mechanistic role of Wilms tumor 1-associated protein in cancer pathogenesis, immunity, immunotherapy, and therapy resistance.Investigational new drugs · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Functional roles, mechanistic insights, and therapeutic potential of the IGF2BP family in viral infections and virus-associated cancers.Journal of molecular histology · 2026Review
- Defining expansions and perturbations to the RNA polymerase III transcriptome and epitranscriptome by modified direct RNA nanopore sequencing.Nature communications · 2026Article
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Targeting serine synthesis pathway to reverse paclitaxel resistance in NSCLC with combination of paclitaxel and anlotinib.Journal of experimental & clinical cancer research : CR · 2026Article
- The "serine code" of metabolic reprogramming: multidimensional roles of the serine synthesis pathway in tumors and novel breakthroughs for targeted therapy.Frontiers in immunology · 2026Review
- Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.Frontiers in immunology · 2026Review
- Resveratrol reverses doxorubicin-resistance and alleviates doxorubicin-induced myocardial injury in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2026Article
- IGF2BP3 redirects glycolytic flux to promote one-carbon metabolism and RNA methylation.Cell reports · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic adaptation serves as a significant driving force for cancer growth and poses a substantial obstacle for cancer therapies. Herein, we unraveled the role of m6A-mediated serine synthesis pathway (SSP) regulation in both hepatocellular carcinoma (HCC) development and therapeutic resistance. We demonstrated that treatment of highly specific m6A inhibitor (STM2457) effectively inhibited HCC cell line growth and suppressed spontaneous HCC formation in mice driven by liver-specific Tp53 knockout and Myc overexpression. Using GLORI-seq, we delineated a single-base-resolution m6A landscape in human HCC cell lines. Interestingly, we identified three core enzymes in the SSP (PHGDH, PSAT1, and PSPH) as novel targets of METTL3-mediated m6A modification. In these SSP genes, m6A modification recruited m6A reader IGF2BP3 to stabilize their mRNA transcripts, thereby enhancing their mRNA and protein expression in HCC cells. Most importantly, our GLORI-seq data revealed that sorafenib-resistant HCC cells elevated m6A modification in SSP genes to promote protein expression and antioxidant production. STM2457 treatment attenuated the serine synthesis pathway, induced oxidative stress, and sensitized HCC cells to sorafenib and lenvatinib treatments. In conclusion, our findings suggest that targeting m6A could be a potential therapeutic strategy for HCC treatment.
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