{
  "abstract": "Deciphering cancer metabolic reprogramming mechanisms can identify new targets to potentiate EZH2 inhibitor efficacy. Using an in vivo genome-wide CRISPR loss-of-function screen in a CRC mouse model, we pinpointed IDO1 as a key mediator of EZH2 inhibitor resistance. EZH2 blockade remodeled CRC cell metabolism by upregulating IDO1 protein and hyperactivating the tryptophan-kynurenine pathway. Both genetic and pharmacological inhibition of IDO1 suppressed tumor growth and rescued EZH2 inhibitor resistance in vitro and in vivo . Mechanistically, EZH2 directly binds and methylates IDO1. Methylation of IDO1 facilitates IDO1 ubiquitination and subsequent degradation. Accordingly, EZH2 inhibition stabilizes IDO1, augments tryptophan-kynurenine metabolic flux, and ultimately confers therapeutic resistance. In summary, our study identifies IDO1 as a non-histone substrate of EZH2 methyltransferase activity and validates that disrupting IDO1-mediated tryptophan metabolism is a viable strategy to overcome EZH2 targeted therapy resistance in cancers.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Yuanjun Tang"
    },
    {
      "name": "Zhanya Huang"
    },
    {
      "name": "Yiting Jia"
    },
    {
      "name": "Yunyun Guo"
    },
    {
      "name": "Xuedi Cao"
    },
    {
      "name": "Renjing Jin"
    },
    {
      "name": "Qianqian Yin"
    },
    {
      "name": "Jiagui Song"
    },
    {
      "name": "Huiguang Chen"
    },
    {
      "name": "Xintong Zhang"
    },
    {
      "name": "Xin Zhou"
    },
    {
      "name": "Rui Cheng"
    },
    {
      "name": "Jianling Yang"
    },
    {
      "name": "Zhengyang Guo",
      "orcid": "0000-0002-8129-2046"
    },
    {
      "name": "Pengcheng Bu",
      "orcid": "0000-0002-3208-0354"
    },
    {
      "name": "Lixiang Xue"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4t1xv9z1r2f6k.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.118237",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2211124726013161",
  "id": "4t1xv9z1r2f6k",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726013161",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-01",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/4t1xv9z1r2f6k.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:21:15Z",
      "native_id": "10.1016/j.celrep.2026.118237",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2211124726013161"
    },
    {
      "first_seen": "2026-11-06T14:21:05Z",
      "native_id": "0a39f6053ac1499b91226ba68c9ac947",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.celrep.2026.118237"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "lcc:QH301-705.5",
      "subfield": "general"
    }
  ],
  "title": "IDO1 methylation by EZH2 confers resistance to its targeted therapy in colorectal cancer through tryptophan-kynurenine metabolic rewiring",
  "title_text": "IDO1 methylation by EZH2 confers resistance to its targeted therapy in colorectal cancer through tryptophan-kynurenine metabolic rewiring",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T14:20:18Z",
  "url": "https://research.draconitic.com/paper/4t1xv9z1r2f6k",
  "venue": "Cell Reports",
  "versions": []
}