ArticleCancer letters2016
Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- H3K36me2 methyltransferase NSD2/WHSC1 promotes triple-negative breast cancer metastasis via activation of ULK1-dependent autophagy.Autophagy · 2025Article
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- KHDRBS1 regulates the pentose phosphate pathway and malignancy of GBM through SNORD51-mediated polyadenylation of ZBED6 pre-mRNA.Cell death & disease · 2024Article
- Analysis of the interlink between glucose-6-phosphate dehydrogenase (G6PD) and lung cancer through multi-omics databases.Heliyon · 2024Article
- Article
- Disulfidptosis, A Novel Cell Death Pathway: Molecular Landscape and Therapeutic Implications.Aging and disease · 2024Review
- NSD family proteins: Rising stars as therapeutic targets.Cell insight · 2024Review
- Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism.Frontiers in genetics · 2024Review
- Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers.International journal of molecular sciences · 2023Review
- N6-methyladenosine methylation in kidney injury.Clinical epigenetics · 2023Review
- The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells.International journal of molecular sciences · 2023Review
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- JMJD5 inhibits lung cancer progression by regulating glucose metabolism through the p53/TIGAR pathway.Medical oncology (Northwood, London, England) · 2023Article
- Targeting glucose-6-phosphate dehydrogenase by 6-AN induces ROS-mediated autophagic cell death in breast cancer.The FEBS journal · 2023Article
- Progesterone Receptor-Mediated Regulation of Cellular Glucose andJournal of the Endocrine Society · 2022Article
- Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma.Cancer science · 2022Article
- Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders.International journal of molecular sciences · 2022Review
- Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2022Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Metabolic reprogramming such as the aerobic glycolysis or Warburg effect is well recognized as a common feature of tumorigenesis. However, molecular mechanisms underlying metabolic alterations for tumor therapeutic resistance are poorly understood. Through gene expression profiling analysis we found that histone H3K36 methyltransferase NSD2/MMSET/WHSC1 expression was highly elevated in tamoxifen-resistant breast cancer cell lines and clinical tumors. IHC analysis indicated that NSD2 protein overexpression was associated with the disease recurrence and poor survival. Ectopic expression of NSD2 wild type, but not the methylase-defective mutant, drove endocrine resistance in multiple cell models and xenograft tumors. Mechanistically, NSD2 was recruited to and methylated H3K36me2 at the promoters of key glucose metabolic enzyme genes. Its overexpression coordinately up-regulated hexokinase 2 (HK2) and glucose-6-phosphate dehydrogenase (G6PD), two key enzymes of glycolysis and the pentose phosphate pathway (PPP), as well as TP53-induced glycolysis regulatory phosphatase TIGAR. Consequently, NSD2-driven tamoxifen-resistant cells and tumors displayed heightened PPP activity, elevated NADPH production, and reduced ROS level, without significantly altered glycolysis. These results illustrate a coordinated, epigenetic activation of key glucose metabolic enzymes in therapeutic resistance and nominate methyltransferase NSD2 as a potential therapeutic target for endocrine resistant breast cancer.
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Registered trials
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