ArticleThe Journal of pathology2018
Menin regulates the serine biosynthetic pathway in Ewing sarcoma.
Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- PHGDH at the crossroads: metabolic plasticity, metastatic paradoxes, and therapeutic reconnaissance in cancer.Journal of biomedical science · 2026Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- Menin inhibitor MI-503 exhibits potent anti-cancer activity in osteosarcoma.Scientific reports · 2025Article
- PHGDH Induction by MAPK Is Essential for Melanoma Formation and Creates an Actionable Metabolic Vulnerability.Cancer research · 2025Article
- Menin in Cancer.Genes · 2024Review
- MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.bioRxiv : the preprint server for biology · 2024Article
- Phosphoserine aminotransferase deficiency diagnosed by whole-exome sequencing and LC-MS/MS reanalysis: A case report and review of literature.Molecular genetics & genomic medicine · 2024Review
- Pharmacological inhibition of the mixed lineage leukemia 1-menin interaction aggravates acute kidney injury induced by folic acid and ischemia-reperfusion in mice.American journal of physiology. Renal physiology · 2023Article
- Study on the Intervention Mechanism of Cryptotanshinone on Human A2780 Ovarian Cancer Cell Line Using GC-MS-Based Cellular Metabolomics.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Menin-MLL1 Interaction Small Molecule Inhibitors: A Potential Therapeutic Strategy for Leukemia and Cancers.Molecules (Basel, Switzerland) · 2023Review
- Hypothalamic Menin regulates systemic aging and cognitive decline.PLoS biology · 2023Article
- Targeting allosteric regulation of cancer metabolism.Nature chemical biology · 2022Review
- Amino acid metabolism in primary bone sarcomas.Frontiers in oncology · 2022Review
- Cancer predisposition genes in Japanese children with rhabdomyosarcoma.Journal of human genetics · 2022Article
- Ailanthone Inhibits Proliferation, Migration and Invasion of Osteosarcoma Cells by Downregulating the Serine Biosynthetic Pathway.Frontiers in oncology · 2022Article
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma.Molecular cancer research : MCR · 2021Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Developmental transcription programs are epigenetically regulated by multi-protein complexes, including the menin- and MLL-containing trithorax (TrxG) complexes, which promote gene transcription by depositing the H3K4me3 activating mark at target gene promoters. We recently reported that in Ewing sarcoma, MLL1 (lysine methyltransferase 2A, KMT2A) and menin are overexpressed and function as oncogenes. Small molecule inhibition of the menin-MLL interaction leads to loss of menin and MLL1 protein expression, and to inhibition of growth and tumorigenicity. Here, we have investigated the mechanistic basis of menin-MLL-mediated oncogenic activity in Ewing sarcoma. Bromouridine sequencing (Bru-seq) was performed to identify changes in nascent gene transcription in Ewing sarcoma cells, following exposure to the menin-MLL interaction inhibitor MI-503. Menin-MLL inhibition resulted in early and widespread reprogramming of metabolic processes. In particular, the serine biosynthetic pathway (SSP) was the pathway most significantly affected by MI-503 treatment. Baseline expression of SSP genes and proteins (PHGDH, PSAT1, and PSPH), and metabolic flux through the SSP were confirmed to be high in Ewing sarcoma. In addition, inhibition of PHGDH resulted in reduced cell proliferation, viability, and tumor growth in vivo, revealing a key dependency of Ewing sarcoma on the SSP. Loss of function studies validated a mechanistic link between menin and the SSP. Specifically, inhibition of menin resulted in diminished expression of SSP genes, reduced H3K4me3 enrichment at the PHGDH promoter, and complete abrogation of de novo serine and glycine biosynthesis, as demonstrated by metabolic tracing studies with
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Registered trials
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