{
  "abstract": "KRASG12D/TP53R175H mutations are hallmarks of malignant tumor progression and are associated with lymph node (LN) metastasis in solid tumor. Nevertheless, the mechanisms underlying KRASG12D/TP53R175H co‐mutation‐mediated LN metastasis remain unclear. Herein, we developed KRASG12D/TP53R175H mutation‐related orthotopic xenograft models and demonstrated that KRASG12D/TP53R175H co‐mutation promotes the lymphangiogenesis and LN metastasis. FUS is identified by next generation sequencing to be upregulated in tumor tissues harbouring KRASG12D/TP53R175H co‐mutation across multi‐center cohorts, wherein KRASG12D‐mediated phosphorylation of TP53R175H promotes FUS transcriptional activation. Functionally, FUS‐mediated extracellular vesicle (EV) promotes lymphangiogenesis and LN metastasis in vitro and in vivo. Mechanistically, upon KRASG12D/TP53R175H co ‑ mutation, FUS regulated circSCARNA10 biosynthesis and promotes EVs secretion by stabilizing RAB3B mRNA, leading to VEGFR3 transcription in lymphatic endothelial cells to trigger lymphangiogenesis and LN metastasis. Blockade of FUS inhibits LN metastasis in KrasG12D/+Trp53R172H/+Pdx‐1‐Cre (KPC) mice model. Clinically, detecting circSCARNA10 in serum‐EVs exhibited higher diagnostic efficiency compared with traditional biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9) in distinguishing LN metastasis. Collectively, we highlight the precise mechanisms by which KRASG12D/TP53R175H co‐mutation mediates EV secretion to trigger LN metastasis, providing a potential therapeutic target for KRASG12D/TP53R175H co‐mutation ‐ driven LN metastasis.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University",
    "Sun Yat‐sen Memorial Hospital Sun Yat‐sen University",
    "The Eighth Affiliated Hospital of Sun Yat‐Sen University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiabin Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuming Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Zhou"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingjie An"
    },
    {
      "affs": [
        1
      ],
      "name": "Mingrui Pang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhihua Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingyu Xie"
    },
    {
      "affs": [
        1
      ],
      "name": "Hanhao Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhou Fang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yao Kong"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yan Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Dingwen Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bingxin Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoming Zhong"
    },
    {
      "affs": [
        1
      ],
      "name": "Changhao Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Rufu Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17wn9jsm350c4.bib",
  "cited_by": 0,
  "doi": "10.1002/jev2.70383",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653645/?tool=EBI",
  "id": "17wn9jsm350c4",
  "issns": [
    "2001-3078"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13653645",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH573-671"
    ],
    [
      "openalex",
      "2730|Lymphatic System and Diseases"
    ]
  ],
  "openalex": "W7221329095",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653645/pdf/?tool=EBI",
  "pmcid": "PMC13653645",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/17wn9jsm350c4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "PMC:PMC13653645",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13653645"
    },
    {
      "first_seen": "2026-10-30T13:47:11Z",
      "native_id": "ab89d0d70ed4406eaa8c64dc7f8b77e0",
      "source": "doaj",
      "url": "https://doi.org/10.1002/jev2.70383"
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  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Lymphatic System and Diseases",
      "subfield": "oncology"
    }
  ],
  "title": "MVB Maturation Responsive to KRASG12D/TP53R175H Co‐mutations Fuels Extracellular Vesicle‐hypersecretion Phenotype to Aggravate Lymphangiogenesis and Lymphatic Metastasis",
  "title_text": "MVB Maturation Responsive to KRASG12D/TP53R175H Co‐mutations Fuels Extracellular Vesicle‐hypersecretion Phenotype to Aggravate Lymphangiogenesis and Lymphatic Metastasis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:11Z",
  "url": "https://research.draconitic.com/paper/17wn9jsm350c4",
  "venue": "Journal of extracellular vesicles",
  "versions": []
}