{
  "abstract": "The atypical cyclin-dependent kinase subfamily (CDK14–18) encompasses five related proteins with unclear function, and for which individual depletion has not demonstrated sustained therapeutic relevance. We report here that CDK16 and CDK18 compensate each other and liver cancer cells are sensitive to the concomitant inactivation of both kinases, resulting in persistent defects in DNA repair and subsequent cell death. These effects are linked to a role of CDK16/18 in regulating nucleocytoplasmatic transport through phosphorylation of nuclear pore complex components, including NUP35. Genetic ablation of Cdk16 and Cdk18 in established liver tumors driven by MYC and beta-catenin oncogenes triggers DNA damage in cancer cells without affecting adjacent normal tissue, ultimately leading to tumor regression. Collectively, these findings provide a rationale for the development of CDK16–18 inhibitors—likely targeting multiple subfamily members due to their structural similarity—as a strategy against aggressive cancers, such as hepatocellular carcinoma, where effective treatment options remain limited.",
  "abstract_shown": true,
  "affiliations": [
    "Cell Division and Cancer group, Molecular Oncology program, Spanish National Cancer Research Center, Madrid 28029, Spain",
    "Cancer Cell Cycle group, Systems Oncology program, Vall d’Hebron Institute of Oncology, Barcelona 08035, Spain",
    "Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, Madrid 28029, Spain",
    "Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan",
    "Confocal Microscopy Unit, Biotechnology program, Spanish National Cancer Research Center, Madrid 28029, Spain",
    "Proteomics Unit, Biotechnology program, Spanish National Cancer Research Center, Madrid 28029, Spain",
    "Division of Molecular Pathophysiology, Medical University, Innsbruck 6020, Austria",
    "Mouse Gene Editing Unit, Biotechnology program, Spanish National Cancer Research Center, Madrid 28029, Spain",
    "Department of Biochemistry and Molecular Biophysics, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California in San Diego, La Jolla, CA 92093-0657",
    "Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305",
    "Pfizer Centers for Therapeutic Innovation, Pfizer Inc.,, New York, NY 10016",
    "Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029",
    "Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029",
    "The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029",
    "Graduate School of Biomedical Sciences at Icahn School of Medicine at Mount Sinai, New York, NY 10029",
    "Institut Català de Recerca i Estudis Avançats, Barcelona 08010, Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Diego Martínez-Alonso"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Enrique Nogueira"
    },
    {
      "affs": [
        0
      ],
      "name": "Luis R. López-Sainz"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexis P. Pérez"
    },
    {
      "affs": [
        0
      ],
      "name": "Carolina Villarroya-Beltri",
      "orcid": "0000-0003-2284-4020"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alejandro Garcia-Diaz",
      "orcid": "0009-0003-6818-1450"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Gloria C. Bonel-Pérez",
      "orcid": "0000-0001-6546-3039"
    },
    {
      "affs": [
        0
      ],
      "name": "Aicha El Bakkali",
      "orcid": "0000-0001-9261-8761"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Senn Wakahashi",
      "orcid": "0000-0001-9197-1790"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Agustín Sánchez-Belmonte"
    },
    {
      "affs": [
        1
      ],
      "name": "Isabel García-Cao",
      "orcid": "0000-0002-4582-0403"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jesus Castillo-Sanchez",
      "orcid": "0009-0008-7011-2020"
    },
    {
      "affs": [
        0
      ],
      "name": "José González-Martínez",
      "orcid": "0000-0002-3850-6803"
    },
    {
      "affs": [
        4
      ],
      "name": "Diego Megias"
    },
    {
      "affs": [
        5
      ],
      "name": "Jana Sánchez"
    },
    {
      "affs": [
        6
      ],
      "name": "Stephan Geley"
    },
    {
      "affs": [
        5
      ],
      "name": "Javier Muñoz"
    },
    {
      "affs": [
        7
      ],
      "name": "Sagrario Ortega",
      "orcid": "0000-0002-1865-7102"
    },
    {
      "affs": [
        8
      ],
      "name": "Fleur M. Ferguson",
      "orcid": "0000-0003-4091-7617"
    },
    {
      "affs": [
        9
      ],
      "name": "Nathanael S. Gray",
      "orcid": "0000-0001-5354-7403"
    },
    {
      "affs": [
        10
      ],
      "name": "David J. Shields"
    },
    {
      "affs": [
        11,
        12,
        13,
        14
      ],
      "name": "Amaia Lujambio",
      "orcid": "0000-0002-2798-1481"
    },
    {
      "affs": [
        0
      ],
      "name": "Guillermo de Cárcer",
      "orcid": "0000-0002-3220-1785"
    },
    {
      "affs": [
        0,
        1,
        2,
        15
      ],
      "name": "Marcos Malumbres",
      "orcid": "0000-0002-0829-6315"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f25k712tckcvt.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2529474123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732246/",
  "id": "f25k712tckcvt",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2529474123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "409"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Cell Biology"
    ],
    [
      "openalex",
      "2730|Cancer-related Molecular Pathways"
    ]
  ],
  "openalex": "W7224088136",
  "pdf_url": null,
  "pmcid": "PMC13732246",
  "pmid": "42949956",
  "published": "2026-10-28",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/f25k712tckcvt.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:16Z",
      "native_id": "PMC13732246",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2529474123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell Biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Functional redundancy between atypical CDKs reveals a vulnerability in hepatocellular carcinoma",
  "title_text": "Functional redundancy between atypical CDKs reveals a vulnerability in hepatocellular carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:16Z",
  "url": "https://research.draconitic.com/paper/f25k712tckcvt",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}