{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:50:41Z","timestamp":1791625841860,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Project of China","award":["2023YFF0613603"],"award-info":[{"award-number":["2023YFF0613603"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22202167"],"award-info":[{"award-number":["22202167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22202167"],"award-info":[{"award-number":["22202167"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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-\u03b2:TGFBR2 signaling. ADAMTS3 knockdown increased extracellular TGF-\u03b2 and downstream SMAD phosphorylation. Neutralization of extracellular TGF-\u03b2 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\u221212 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.<\/jats:p>","DOI":"10.3390\/cells15191784","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:19Z","timestamp":1790773279000},"page":"1784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-\u03b2:TGFBR2 Signaling"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9633-8879","authenticated-orcid":false,"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"College of Optical and Electronic Technology, China Jiliang University, Hangzhou 310018, 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Engineering, Zhejiang University, Hangzhou 310027, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Yaosen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Optical and Electronic Technology, China Jiliang University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-1510","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Maccaferri","sequence":"additional","affiliation":[{"name":"Ultrafast Nanoscience Group, Department of Physics, Ume\u00e5 University, Linnaeus v\u00e4g 24, 901 87 Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Centre for Microbial Research, Ume\u00e5 University, Linnaeus v\u00e4g 24, 901 87 Ume\u00e5, Sweden"},{"name":"Wallenberg Initiative Materials Science for Sustainability, Department of Physics, Ume\u00e5 University, Linnaeus v\u00e4g 24, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Ali","family":"Douaki","sequence":"additional","affiliation":[{"name":"Optoelectronic Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy"},{"name":"Dipartimento di Scienze e Metodi dell\u2019Ingegneria, Universit\u00e0 degli Studi di Modena e Reggio Emilia, Viale Amendola 2, 14122 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jianguo","family":"Feng","sequence":"additional","affiliation":[{"name":"Experimental Research Center, Zhejiang Cancer Hospital, Hangzhou 310022, 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