ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling
10 affiliations
- 1College of Optical and Electronic Technology, China Jiliang University, Hangzhou 310018, China
- 2Key Laboratory of Quantum Precision Measurement, College of Physics, Zhejiang University of Technology, Hangzhou 310018, China
- 3Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, China
- 4College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China
- 5Ultrafast Nanoscience Group, Department of Physics, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden
- 6Umeå Centre for Microbial Research, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden
- 7Wallenberg Initiative Materials Science for Sustainability, Department of Physics, Umeå University, Linnaeus väg 24, 901 87 Umeå, Sweden
- 8Optoelectronic Department, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy
- 9Dipartimento di Scienze e Metodi dell’Ingegneria, Università degli Studi di Modena e Reggio Emilia, Viale Amendola 2, 14122 Reggio Emilia, Italy
- 10Experimental Research Center, Zhejiang Cancer Hospital, Hangzhou 310022, China
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.
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BibTeX
@article{wang2026adamts3,
title = {{ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling}},
author = {Chen Wang and Huaizhou Jin and Qijie Zhang and Yanqiu Zou and Yaosen Wang and Nicolò Maccaferri and Ali Douaki and Jianguo Feng and Denis Garoli and Shangzhong Jin},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191784},
url = {https://europepmc.org/article/PMC/PMC13664179},
note = {CC BY},
}
RIS
TY - JOUR
TI - ADAMTS3 Promotes Hepatocellular Carcinoma Cell Growth and Migration Through TGF-β:TGFBR2 Signaling
AU - Chen Wang
AU - Huaizhou Jin
AU - Qijie Zhang
AU - Yanqiu Zou
AU - Yaosen Wang
AU - Nicolò Maccaferri
AU - Ali Douaki
AU - Jianguo Feng
AU - Denis Garoli
AU - Shangzhong Jin
PY - 2026
DA - 2026/09/30
JO - Cells
DO - 10.3390/cells15191784
UR - https://europepmc.org/article/PMC/PMC13664179
AB - 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.
SN - 2073-4409
ER -