{
  "abstract": "Cancer cell plasticity underlies tumor progression, metastasis and therapeutic resistance, yet how RNA-binding proteins regulate malignant state transitions remains poorly defined. Here, we identify the splicing regulator RBFOX2 as a suppressor of oncogenic cell plasticity in Group 3 medulloblastoma (MB). OTX2 antagonizes RBFOX2 by directing an opposing alternative splicing program that mirrors developmental origins and controls cytoskeletal dynamics and cell state transitions. Mechanistically, OTX2 alters the RBFOX2 RNA-binding landscape, limiting RBFOX2 engagement at cytoskeletal loci and suppressing exon inclusion. RBFOX2 loss rewires splicing and transcriptional outputs to promote highly plastic proliferative, mesenchymal-like and undifferentiated cellular states associated with enhanced oncogenic properties. Consistent with these findings, RBFOX2low states mark highly plastic cell populations in patient tumors and xenografts, positioning RBFOX2 as a determinant of malignant cell stability. Together, these findings establish RBFOX2 as a developmental gatekeeper that restrains malignant cell plasticity through coordinated control of cytoskeletal gene programs.",
  "abstract_shown": true,
  "affiliations": [
    "Baylor College of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "R. K. Sah"
    },
    {
      "name": "X. Yan"
    },
    {
      "name": "L. Louis"
    },
    {
      "name": "N. Gonzales"
    },
    {
      "name": "U. Tsogt"
    },
    {
      "name": "B. He"
    },
    {
      "name": "L. G. Hoefner"
    },
    {
      "name": "L. Lecomte"
    },
    {
      "name": "M. Bartels"
    },
    {
      "name": "C. A. Le Roux"
    },
    {
      "name": "A. C. Starner"
    },
    {
      "name": "I. Basili"
    },
    {
      "name": "O. Ayrault"
    },
    {
      "name": "E. L. Van Nostrand"
    },
    {
      "name": "O. Saulnier"
    },
    {
      "name": "J. Zagozewski"
    },
    {
      "affs": [
        0
      ],
      "name": "T. E. Werbowetski-Ogilvie"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2ajak31hvv92g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.756284",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756284v1.full",
  "id": "2ajak31hvv92g",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756284v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W7220651583",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756284v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2ajak31hvv92g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:11Z",
      "native_id": "10.64898/2026.10.02.756284",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756284v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "RBFOX2 restrains oncogenic cell plasticity in Group 3 medulloblastoma",
  "title_text": "RBFOX2 restrains oncogenic cell plasticity in Group 3 medulloblastoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:11Z",
  "url": "https://research.draconitic.com/paper/2ajak31hvv92g",
  "venue": "bioRxiv",
  "versions": []
}