{
  "abstract": "Glioblastoma (GBM) is characterized by near-universal recurrence and resistance to therapy. Although tumor-intrinsic mechanisms of radiation resistance have been extensively studied, how the extracellular matrix influences signaling in radiation-resistant GBM remains poorly understood. Here, we investigated discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, using matched radiation-sensitive parental and radiation-resistant patient-derived GBM models generated through serial in vivo irradiation. Within a three-dimensional collagen I matrix, radiation-resistant GBM cells exhibited distinct temporal patterns of Ki-67 positivity and ERK1/2 phosphorylation compared with parental cells. Despite increased DDR1 expression, radiation-resistant cells exhibited markedly reduced DDR1 phosphorylation and enhanced ectodomain shedding, characterized by accumulation of the membrane-associated C-terminal fragment and release of the N-terminal fragment. DDR1 depletion reduced ERK1/2 phosphorylation, supporting its contribution to ERK1/2 signaling under these conditions. ADAMTS1 was markedly upregulated in radiation-resistant cells, and its knockdown reduced DDR1 ectodomain shedding while increasing full-length DDR1 abundance, ERK1/2 and RB phosphorylation, cyclin D1 expression, and Ki-67 positivity. Together, these findings reveal a distinct DDR1 regulatory state in acquired radiation-resistant GBM, characterized by enhanced ADAMTS1-associated ectodomain shedding, reduced receptor phosphorylation, and attenuated proliferative signaling within a three-dimensional collagen I matrix.",
  "abstract_shown": true,
  "affiliations": [
    "University of Alabama at Birmingham"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "S. Dunlap"
    },
    {
      "name": "C. A. Harvey"
    },
    {
      "name": "A. Elkholy"
    },
    {
      "name": "L. Gehrs"
    },
    {
      "name": "M. Mohamed"
    },
    {
      "name": "S. Zakakhosravi"
    },
    {
      "name": "T. L. Schanel"
    },
    {
      "name": "J. M. Murphy"
    },
    {
      "name": "S. T. S. Lim"
    },
    {
      "name": "C. D. Willey"
    },
    {
      "affs": [
        0
      ],
      "name": "E.-Y. E. Ahn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0t2334r5dm49w.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757755",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757755v1.full",
  "id": "0t2334r5dm49w",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757755v1",
  "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",
      "2716|Glioma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7221120471",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757755v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0t2334r5dm49w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:52Z",
      "native_id": "10.64898/2026.10.08.757755",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757755v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Collagen-dependent DDR1 ectodomain shedding regulates proliferative signaling in radiation-resistant glioblastoma",
  "title_text": "Collagen-dependent DDR1 ectodomain shedding regulates proliferative signaling in radiation-resistant glioblastoma",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:52Z",
  "url": "https://research.draconitic.com/paper/0t2334r5dm49w",
  "venue": "bioRxiv",
  "versions": []
}