{
  "abstract": "Cross-resistance to chemotherapy and radiotherapy is a major obstacle in cancer treatment and strongly associated with poor prognosis. Particularly, oral squamous cell carcinoma (OSCC) frequently exhibits such cross-resistance, limiting the efficacy of standard chemoradiotherapy. To unveil its molecular mechanism, we took advantage of a comprehensive proteomic analysis using clinically relevant radio-resistant OSCC cells, and identified distinct alterations in protein expression. Among the differentially expressed proteins, we focused on the down-regulation of cylindromatosis (CYLD), a deubiquitinating enzyme and tumor suppressor. Suppression of CYLD expression in OSCC cells led to accumulation of DNA damage and increased cross-resistance. CYLD down-regulation caused cross-resistance in OSCC cells, at least in part, via NF-κB hyperactivation. Notably, EGFR-TKI monotherapy demonstrated significant efficacy against cross-resistant OSCC in vitro and in vivo. Moreover, in patient-derived xenograft (PDX) models, CYLD expression might serve as a potential predictive biomarker for EGFR-TKI responsiveness in cross-resistant OSCC. These findings highlight the pivotal role of CYLD down-regulation driving OSCC progression via cross-resistance and offer new prospects for the clinical application of EGFR-TKIs, with CYLD expression serving as a potential predictive biomarker for OSCC patient with cross-resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.",
    "Institute for Advanced Biosciences, Keio University, 403-1 Nihonkoku, Daiboji, Tsuruoka-shi, Yamagata 997-0017, Japan.",
    "Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811 Japan.",
    "Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556 Japan.",
    "Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino, Sendai, Miyagi, Japan.",
    "Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.",
    "Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kou Yonemaru"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoki Suenaga"
    },
    {
      "affs": [
        1
      ],
      "name": "Takeshi Masuda"
    },
    {
      "affs": [
        2
      ],
      "name": "Ryusho Kariya"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuki Seki"
    },
    {
      "affs": [
        3
      ],
      "name": "Ryoji Yoshida"
    },
    {
      "affs": [
        3
      ],
      "name": "Hideki Nakayama"
    },
    {
      "affs": [
        4
      ],
      "name": "Yoshikazu Kuwahara"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Fumihiro Nishimura"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Kazutaka Oda"
    },
    {
      "affs": [
        6
      ],
      "name": "Jian-Dong Li"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Hirofumi Jono"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dbrhshcdf1ymp.bib",
  "cited_by": 0,
  "doi": "10.7150/ijbs.138201",
  "fulltext_url": "https://europepmc.org/articles/PMC13686046",
  "id": "dbrhshcdf1ymp",
  "issns": [
    "1449-2288"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910291",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2733|Head and Neck Cancer Studies"
    ]
  ],
  "openalex": "W7221465755",
  "pdf_url": "https://europepmc.org/articles/PMC13686046?pdf=render",
  "pmcid": "PMC13686046",
  "pmid": "42910291",
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dbrhshcdf1ymp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42910291",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910291"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2733|Head and Neck Cancer Studies",
      "subfield": "general"
    }
  ],
  "title": "CYLD: A Key Factor and Novel Predictive Biomarker of Cross-Resistance to Chemotherapy and Radiotherapy in Oral Squamous Cell Carcinoma.",
  "title_text": "CYLD: A Key Factor and Novel Predictive Biomarker of Cross-Resistance to Chemotherapy and Radiotherapy in Oral Squamous Cell Carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/dbrhshcdf1ymp",
  "venue": "International journal of biological sciences",
  "versions": []
}