{
  "abstract": "Metastasis is the primary cause of mortality in cancer including lung adenocarcinoma (LUAD), yet the underlying mechanisms remain incompletely understood. Preferentially expressed antigen of melanoma (PRAME), a cancer-testis antigen, displays context-dependent functions across malignancies, but its biological role in LUAD metastasis has not been clearly defined. Here, we demonstrate that the significantly upregulated PRAME in metastatic LUAD directly interacts with the m⁶A methyltransferase METTL3 and promotes its K63-linked non-proteolytic ubiquitination. This modification occurs at lysine 235 of METTL3, increases its protein stability and facilitates METTL3 interaction with METTL14 and WTAP. Consequently, m⁶A modification of TGFB2 mRNA and activation of the TGF-β signaling pathway are enhanced, which is essential for PRAME-driven pro-metastatic effects both in vitro and in vivo. Clinically, PRAME expression positively correlates with METTL3 protein abundance and TGF-β pathway activation, and is robustly associated with poor clinical outcomes. Taken together, our findings identify K63-linked ubiquitination as a previously unrecognized post-translational modification of METTL3 and underscore the importance of the PRAME/METTL3/TGF-β axis in LUAD metastasis, providing mechanistic insights and potential therapeutic targets for this malignancy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine and Institute of Precise Medicine, The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China.",
    "Zhongshan School of Medicine Sun Yat-Sen University Guangzhou Guangdong China.",
    "Cancer Institute, School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong China.",
    "Clinical Experimental Center, Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational Research Jiangmen Central Hospital Jiangmen Guangdong China.",
    "Department of Neurosurgery Jiangmen Central Hospital Jiangmen Guangdong China.",
    "Sun Yat-sen University Cancer Center Guangzhou Guangdong China.",
    "Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China.",
    "State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences University of Macau Macau SAR China.",
    "Department of Endocrinology and Diabetes Center, The First Affiliated Hospital Sun Yat-sen University Guangzhou China.",
    "State Key Laboratory of Multi-Organ Injury Prevention and Treatment Southern Medical University Guangzhou Guangdong China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xia Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Xuemei Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yaxuan Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiamei Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiyu Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiaorui Bai"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiuqiao Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Shujun Liang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiang Dong"
    },
    {
      "affs": [
        3
      ],
      "name": "Xin Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiyong Gu"
    },
    {
      "affs": [
        5
      ],
      "name": "Shuqin Dai"
    },
    {
      "affs": [
        6
      ],
      "name": "Hongchun Du"
    },
    {
      "affs": [
        7
      ],
      "name": "Meiwan Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Tianyu Tao"
    },
    {
      "affs": [
        8
      ],
      "name": "Hongyu Guan"
    },
    {
      "affs": [
        1
      ],
      "name": "Jueheng Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Han Tian"
    },
    {
      "affs": [
        1
      ],
      "name": "Junchao Cai"
    },
    {
      "affs": [
        2,
        1,
        9
      ],
      "name": "Mengfeng Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Xu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4zfvzwz7v0d14.bib",
  "cited_by": 0,
  "doi": "10.1002/mco2.71066",
  "fulltext_url": "https://europepmc.org/articles/PMC13679842",
  "id": "4zfvzwz7v0d14",
  "issns": [
    "2688-2663"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899254",
  "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",
      "1312|RNA modifications and cancer"
    ]
  ],
  "openalex": "W7222927399",
  "pdf_url": "https://europepmc.org/articles/PMC13679842?pdf=render",
  "pmcid": "PMC13679842",
  "pmid": "42899254",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4zfvzwz7v0d14.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42899254",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899254"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA modifications and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "PRAME Augments K63-Linked Ubiquitination and Stabilization of METTL3 to Promote Lung Adenocarcinoma Metastasis.",
  "title_text": "PRAME Augments K63-Linked Ubiquitination and Stabilization of METTL3 to Promote Lung Adenocarcinoma Metastasis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/4zfvzwz7v0d14",
  "venue": "MedComm",
  "versions": []
}