{
  "abstract": "Cisplatin resistance is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). To address this challenge, we screened a U.S. Food and Drug Administration (FDA)-approved drug library and identified fingolimod, an immunomodulatory agent, as a potent inhibitor of cisplatin-resistant ESCC cells. Fingolimod is likely to directly binds to Glu266 of the nuclear pore complex protein NUP54, promoting its proteasomal degradation. This disrupts the NUP54-NUP58-NUP62 central channel, impairing the nuclear import of the key DNA repair protein SPIDR. Consequently, fingolimod treatment inhibits the recruitment of the SPIDR-RAD51-DMC1 complex by chromatin, causing defective homologous recombination repair, accumulation of DNA damage, and ultimately, the reversal of cisplatin resistance. In addition, fingolimod restored the sensitivity of cisplatin to ESCC treatment in both patient-derived xenograft and organoid models. Our study unveils a novel mechanism by which fingolimod targets the nuclear pore complex to suppress DNA repair, providing a compelling rationale for repurposing fingolimod as a combination therapy to overcome cisplatin resistance in ESCC.",
  "abstract_shown": true,
  "affiliations": [
    "Shaanxi Key Laboratory of Research and Utilization of Resource Plants on the Loess Plateau, College of Life Sciences, Yan'an University, Yan'an, China.",
    "Department of Pathology, Xijing Hospital, School of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China.",
    "Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.",
    "Department of Clinical Medicine, School of Medicine, Yan'an University, Yan'an, China.",
    "Department of Life Sciences, Aberystwyth University, Aberystwyth, UK.",
    "Department of Neurosurgery, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, China. clg201820271@126.com.",
    "The South Campus of the Sixth People's Hospital, Shanghai University of Medicine & Health Sciences, No. 6600 Nanfeng Highway, Shanghai, 201400, China. zhenliang6@126.com.",
    "Department of Reproductive Medicine, Xi'an International Medical Center Hospital, Northwest University, 777 Xitai Road, Xi'an, 710100, China. 361400283@qq.com.",
    "Department of Pathology, Xijing Hospital, School of Basic Medicine, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, China. limingyang1108@sina.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Duo Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Jin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Guoliang Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Tianqi Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiangru Zhou"
    },
    {
      "affs": [
        1
      ],
      "name": "Junpeng Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Pusong Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Peng Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinya Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Luis A J Mur"
    },
    {
      "affs": [
        5
      ],
      "name": "Ligang Chen"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhenliang Sun"
    },
    {
      "affs": [
        7
      ],
      "name": "Qingge Jia"
    },
    {
      "affs": [
        8
      ],
      "name": "Mingyang Li",
      "orcid": "0000-0003-1766-7867"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/caz33xng1z4f3.bib",
  "cited_by": 0,
  "doi": "10.1186/s12964-026-03113-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13718147",
  "id": "caz33xng1z4f3",
  "issns": [
    "1478-811X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958413",
  "language": "eng",
  "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": [
    [
      "heading",
      "Research"
    ],
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      "openalex",
      "2746|Esophageal Cancer Research and Treatment"
    ]
  ],
  "openalex": "W7171985472",
  "pdf_url": "https://europepmc.org/articles/PMC13718147?pdf=render",
  "pmcid": "PMC13718147",
  "pmid": "42958413",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/caz33xng1z4f3.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42958413",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958413"
    },
    {
      "first_seen": "2026-11-02T12:22:16Z",
      "native_id": "PMC13718147",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12964-026-03113-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Esophageal Cancer Research and Treatment",
      "subfield": "surgery"
    }
  ],
  "title": "Fingolimod overcomes cisplatin resistance in esophageal squamous cell carcinoma by targeting NUP54 to disrupt homologous recombination repair.",
  "title_text": "Fingolimod overcomes cisplatin resistance in esophageal squamous cell carcinoma by targeting NUP54 to disrupt homologous recombination repair.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:16Z",
  "url": "https://research.draconitic.com/paper/caz33xng1z4f3",
  "venue": "Cell communication and signaling : CCS",
  "versions": []
}