{
  "abstract": "Cell-cell interactions shape the fate of mutant cells during cancer initiation but how these interactions evolve during progression to pathologically recognizable lesions remain poorly understood. Here, we investigated cell-cell communication during serous endometrial carcinoma (SEC; also known as uterine serous carcinoma) development using a lineage-traceable mouse model and cross-species analyses of the mouse and human neoplastic endometrium. In mice, the early, pre-dysplastic stage was marked by a global decrease in inferred cell-cell interactions, followed by extensive communication network rewiring during neoplastic progression. Pathway-specific analysis revealed a similar pattern for NOTCH signaling, with NOTCH2 emerging as the dominant NOTCH receptor in Trp53/Rb1-mutant immature epithelial cells. Functionally, NOTCH2 promoted the outgrowth of more proliferative mutant organoids. Cross-species transcriptomic analysis identified conserved immature epithelial states in mouse and human neoplastic endometrial epithelium. In human tissues, NOTCH2 was overexpressed in serous endometrial intraepithelial carcinoma, a precursor of SEC, and in overt SEC. Furthermore, elevated NOTCH2 expression was associated with poor patient survival. These findings link cell-cell communication rewiring during experimental SEC development to conserved neoplastic epithelial states and identify NOTCH2 as an early marker and a potential target of disease interception.",
  "abstract_shown": true,
  "affiliations": [
    "Cornell University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "M. G. Pirtz"
    },
    {
      "name": "A. Flesken-Nikitin"
    },
    {
      "name": "C. Q. Ralston"
    },
    {
      "name": "D. J. Phuong"
    },
    {
      "name": "N. Wang"
    },
    {
      "name": "T. Chu"
    },
    {
      "name": "S. Chen"
    },
    {
      "name": "Y. Zheng"
    },
    {
      "name": "E. Schmoeckel"
    },
    {
      "name": "A. Yemelyanova"
    },
    {
      "name": "I.-M. Shih"
    },
    {
      "name": "C. G. Danko"
    },
    {
      "name": "B. D. Cosgrove"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Y. Nikitin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fa5sarcd96pkx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748540",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748540v1.full",
  "id": "fa5sarcd96pkx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748540v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Developmental Biology and Gene Regulation"
    ]
  ],
  "openalex": "W7207672484",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748540v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fa5sarcd96pkx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.64898/2026.09.01.748540",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748540v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Cross-species analysis links cell-cell communication rewiring to NOTCH2 during serous endometrial carcinogenesis",
  "title_text": "Cross-species analysis links cell-cell communication rewiring to NOTCH2 during serous endometrial carcinogenesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:26Z",
  "url": "https://research.draconitic.com/paper/fa5sarcd96pkx",
  "venue": "bioRxiv",
  "versions": []
}