{
  "abstract": "Epithelioid sarcoma (EPS) is an aggressive soft-tissue sarcoma characterized by loss of the chromatin-remodeling subunit SMARCB1. The oncogenic programs driving EPS remain poorly understood. Through CRISPR loss-of-function screens, we identified conserved dependencies on integrin signaling components and cyclin-dependent kinases (CDKs). Genetic disruption of integrin subunit alpha V (ITGAV)-centered signaling impaired epithelioid cluster formation and reduced MYC expression. SMARCB1 re-expression phenocopied these effects and revealed that SMARCB1 loss selectively represses context-dependent integrin subunits while preserving an ITGAV-centered pro-survival axis, associated with altered BAF complex occupancy. Analysis of EPS cell lines and primary tumors revealed frequent genetic or epigenetic inactivation of CDKN2A/p16, indicating that loss of cell-cycle control is a key cooperating event in EPS development and providing a mechanistic rationale for targeting CDK4/6. Together, these findings establish integrin-driven oncogenic signaling coupled with disruption of cell-cycle control as a central oncogenic program in EPS and identify actionable therapeutic vulnerabilities.",
  "abstract_shown": true,
  "affiliations": [
    "Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "R. Miyamoto"
    },
    {
      "name": "J. Park"
    },
    {
      "name": "G. H. Dwosh"
    },
    {
      "name": "V. Zuco"
    },
    {
      "name": "S. Pasquali"
    },
    {
      "name": "B. C. Dickson"
    },
    {
      "affs": [
        0
      ],
      "name": "D. G. Kirsch"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fbh2vs8fdb0wz.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748640",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748640v1.full",
  "id": "fbh2vs8fdb0wz",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748640v1",
  "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|Chromatin Remodeling and Cancer"
    ]
  ],
  "openalex": "W7207765049",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748640v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fbh2vs8fdb0wz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:50Z",
      "native_id": "10.64898/2026.09.01.748640",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748640v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Rewiring of Integrin Signaling and Cell-cycle Deregulation Drive SMARCB1-Deficient Epithelioid Sarcoma",
  "title_text": "Rewiring of Integrin Signaling and Cell-cycle Deregulation Drive SMARCB1-Deficient Epithelioid Sarcoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:50Z",
  "url": "https://research.draconitic.com/paper/fbh2vs8fdb0wz",
  "venue": "bioRxiv",
  "versions": []
}