{
  "abstract": "Nicotinamide adenine dinucleotide (NAD+) metabolism is frequently rewired in cancer, creating metabolic vulnerabilities that can be therapeutically exploited. Loss of nicotinate phosphoribosyltransferase (NAPRT), a rate‐limiting enzyme of the Preiss–Handler pathway, renders tumor cells dependent on nicotinamide phosphoribosyltransferase (NAMPT)‐mediated NAD+ synthesis and serves as a predictive biomarker for NAMPT inhibitor sensitivity. However, whether NAPRT loss actively contributes to tumorigenesis remains unclear. Here, we show that NAPRT depletion promotes tumorigenic phenotypes in lung cancer through a noncanonical mechanism independent of NAD+ biosynthesis. NAPRT knockdown enhanced clonogenic initiation, sphere formation, and invasive capacity. Mechanistically, NAPRT loss drives mTORC2‐dependent activation of the AKT signaling axis. This effect was not reversed by nicotinic acid or NAD+ supplementation or recapitulated by catalytic inhibition of NAPRT, indicating a function distinct from its metabolic role. Pharmacologic AKT inhibition attenuated the enhanced growth induced by NAPRT depletion. In vivo, lung‐specific Naprt deletion significantly increased tumor burden in Kras G12D‐driven mice without altering tumor histology or immune cell composition. Together, these findings identify a previously unrecognized tumor‐suppressive role for NAPRT in lung tumor initiation and growth.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Sciences Yonsei University College of Medicine Seoul Korea",
    "Graduate School of Medical Science, Brain Korea 21 Project Yonsei University College of Medicine Seoul Korea",
    "Division of Cancer Biology, Research Institute National Cancer Center Goyang Korea",
    "Department of Microbiology and Immunology Yonsei University College of Medicine Seoul Korea",
    "Checkmate Therapeutics Inc. Seoul Korea",
    "Graduate Program for Nanomedical Science Yonsei University Seoul Korea",
    "Department of Cancer Biomedical Science National Cancer Center Graduate School of Cancer Science and Policy Goyang Korea"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Myung Joon Oh",
      "orcid": "0000-0002-3676-3718"
    },
    {
      "affs": [
        2
      ],
      "name": "Ji Yun Jang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yoon Jeon"
    },
    {
      "affs": [
        3
      ],
      "name": "Gi‐Cheon Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Hwanho Lee"
    },
    {
      "affs": [
        4
      ],
      "name": "Jooyoung Lee"
    },
    {
      "affs": [
        5
      ],
      "name": "Ju‐Hwa Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Hakhyun Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Minjee Kim"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Ho‐Keun Kwon"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Ho Lee",
      "orcid": "0000-0001-5573-742X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hyun Seok Kim",
      "orcid": "0000-0003-4498-8690"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/38gvzqdv5f8mq.bib",
  "cited_by": 0,
  "doi": "10.1002/1878-0261.70330",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13613957/",
  "id": "38gvzqdv5f8mq",
  "issns": [
    "1574-7891",
    "1878-0261"
  ],
  "landing_url": "https://doi.org/10.1002/1878-0261.70330",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Akt Signalling"
    ],
    [
      "heading",
      "Cancer Metabolism"
    ],
    [
      "heading",
      "Lung Cancer"
    ],
    [
      "heading",
      "Short Report"
    ],
    [
      "openalex",
      "2717|Sirtuins and Resveratrol in Medicine"
    ]
  ],
  "openalex": "W7214377378",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.70330",
  "pmcid": "PMC13613957",
  "pmid": "42788471",
  "published": "2026-09-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/38gvzqdv5f8mq.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:31Z",
      "native_id": "PMC13613957",
      "source": "pmc",
      "url": "https://doi.org/10.1002/1878-0261.70330"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2717|Sirtuins and Resveratrol in Medicine",
      "subfield": "general"
    }
  ],
  "title": "NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD + biosynthesis",
  "title_text": "NAPRT loss promotes lung tumor initiation and growth through AKT signaling independently of NAD + biosynthesis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:00Z",
  "url": "https://research.draconitic.com/paper/38gvzqdv5f8mq",
  "venue": "Molecular Oncology",
  "versions": []
}