{
  "abstract": "IntroductionLung cancer brain metastasis is shaped by reciprocal interactions between tumor cells and the brain microenvironment, yet whether KDM1A/LSD1 influences this communication through tumor-derived extracellular vesicles (EVs) remains unclear.MethodsHere, we combined within-patient single-cell transcriptomic analysis with genetic and pharmacological LSD1 perturbation, EV-based functional assays, and an intracranial xenograft model to define an LSD1-associated tumor-myeloid communication phenotype.ResultsSingle-cell analysis identified a reproducible KDM1A co-expression-associated tumor-cell state characterized by coordinated communication- and microenvironment-remodeling programs and recurrent APP-CD74- and MDK-related signaling patterns. Among the prioritized candidates, MDK showed the most consistent experimental response to LSD1 knockout, with concordant reductions in donor-cell mRNA, cellular protein and EV-associated protein. Functionally, EVs derived from LSD1-deficient tumor cells shifted HMC3 microglia-like cells toward a mixed inflammatory and immunoregulatory state and altered their secretory output. Conditioned medium from these EV-exposed HMC3 cells subsequently suppressed H1299 proliferation and enhanced apoptosis, indicating a secondary tumor-myeloid-tumor paracrine effect. Pharmacological LSD1 inhibition produced a partially overlapping functional phenotype. In mice with established intracranial tumors, LSD1-KO-EV treatment was associated with lower endpoint ex vivo brain bioluminescence, with representative H&E sections showing a qualitatively concordant pattern.DiscussionThese findings support EV-mediated tumor-myeloid communication as one consequence of LSD1 perturbation and nominate MDK-associated EV remodeling for direct mechanistic testing.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Zi-Hao Li"
    },
    {
      "name": "Juan-Juan Peng"
    },
    {
      "name": "Bao-Xin-Zi Liu"
    },
    {
      "name": "Qing-Feng Li"
    },
    {
      "name": "Mian-Hua Wu"
    },
    {
      "name": "Lei Wang"
    },
    {
      "name": "Zhong-Rui Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b995d0r2kzcwh.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1912724",
  "fulltext_url": null,
  "id": "b995d0r2kzcwh",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1912724",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-13",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/b995d0r2kzcwh.ris",
  "sources": [
    {
      "first_seen": "2026-11-13T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1912724",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1912724"
    },
    {
      "first_seen": "2026-11-13T12:20:47Z",
      "native_id": "10.3389/fphar.2026.1912724",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1912724/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "KDM1A-associated tumor–myeloid communication and extracellular vesicle-mediated microglia-like responses in lung cancer brain metastasis",
  "title_text": "KDM1A-associated tumor–myeloid communication and extracellular vesicle-mediated microglia-like responses in lung cancer brain metastasis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:20:47Z",
  "url": "https://research.draconitic.com/paper/b995d0r2kzcwh",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}