{
  "abstract": "Early diagnosis of hepatocellular carcinoma (HCC) still represents a significant challenge, particularly in the context of etiological shift toward obesity and non-viral liver disease-associated HCC. Through intersection-based analysis of independent transcriptomic datasets comprising healthy controls, individuals with obesity or NAFLD, and HCC patients with viral or non-viral etiologies, we prioritized ADAMTS3, a secreted protein, for further investigation of its functional and mechanistic relevance to HCC. ADAMTS3 was upregulated in HCC and demonstrated transcriptomic discrimination between HCC and non-HCC populations. Notably, in the validation cohort, ADAMTS3 retained discriminative capacity in clinically defined alpha-fetoprotein-negative HCC patients. Functionally, ADAMTS3 knockdown impaired cell proliferation, clonogenicity, and migration, while inducing apoptosis and cell-cycle arrest. Reintroduction of ADAMTS3 partially rescued these cellular effects. Mechanistically, ADAMTS3 promotes HCC cell growth and migration through TGF-β:TGFBR2 signaling. ADAMTS3 knockdown increased extracellular TGF-β and downstream SMAD phosphorylation. Neutralization of extracellular TGF-β alleviated growth inhibition caused by ADAMTS3 knockdown. Consistently, TGFBR2 knockdown partially restored the cell growth and migration suppressed by ADAMTS3 knockdown. We also developed a DNA origami-based SERS aptasensor targeting ADAMTS3, achieving highly sensitive detection of ADAMTS3 down to 10−12 M with strong quantitative capability (R2 = 0.914). Together, our findings support a role for ADAMTS3 in promoting HCC cell growth and migration and provide a basis for further investigation of its relevance to HCC biomarker development. The DNA origami-based SERS aptasensor provides a sensitive analytical approach for future studies of circulating or serum ADAMTS3.",
  "abstract_shown": true,
  "affiliations": [
    "College of Optical and Electronic Technology, China Jiliang University, Hangzhou 310018, China",
    "Key Laboratory of Quantum Precision Measurement, College of Physics, Zhejiang University of Technology, Hangzhou 310018, China",
    "Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, China",
    "College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China",
    "Ultrafast Nanoscience Group, Department of Physics, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden",
    "Umeå Centre for Microbial Research, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden",
    "Wallenberg Initiative Materials Science for Sustainability, Department of Physics, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden",
    "Optoelectronic Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy",
    "Dipartimento di Scienze e Metodi dell’Ingegneria, Università degli Studi di Modena e Reggio Emilia, Viale Amendola 2, 14122 Reggio Emilia, Italy",
    "Experimental Research Center, Zhejiang Cancer Hospital, Hangzhou 310022, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chen Wang",
      "orcid": "0009-0001-9633-8879"
    },
    {
      "affs": [
        1
      ],
      "name": "Huaizhou Jin",
      "orcid": "0000-0003-0540-3223"
    },
    {
      "affs": [
        2
      ],
      "name": "Qijie Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Yanqiu Zou",
      "orcid": "0009-0007-3158-0860"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaosen Wang"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Nicolò Maccaferri",
      "orcid": "0000-0002-0143-1510"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Ali Douaki"
    },
    {
      "affs": [
        9
      ],
      "name": "Jianguo Feng"
    },
    {
      "affs": [
        0,
        7,
        8
      ],
      "name": "Denis Garoli",
      "orcid": "0000-0002-5418-7494"
    },
    {
      "affs": [
        0
      ],
      "name": "Shangzhong Jin",
      "orcid": "0000-0003-1219-5709"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0723hdr3qz3y0.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15191784",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664179/?tool=EBI",
  "id": "0723hdr3qz3y0",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13664179",
  "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",
      "2721|Hepatocellular Carcinoma Treatment and Prognosis"
    ]
  ],
  "openalex": "W7214935107",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664179/pdf/?tool=EBI",
  "pmcid": "PMC13664179",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0723hdr3qz3y0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "PMC:PMC13664179",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13664179"
    },
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15191784",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/19/1784"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2073-4409",
      "subfield": "cell-biology"
    }
  ],
  "title": "ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling",
  "title_text": "ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:02Z",
  "url": "https://research.draconitic.com/paper/0723hdr3qz3y0",
  "venue": "Cells",
  "versions": []
}