ADAMTS1, short for A Disintegrin and Metalloprotease with Thrombospondin Motifs 1, is a matrix metalloproteinase. It has been implicated in various physiological and pathological processes. Functionally, it can interact with molecules like VEGF, influencing angiogenesis-a crucial process in tumor growth and development. It is also associated with pathways such as Notch1-SOX2, which play roles in stemness properties and tumor invasion [1,2].

In glioma, ADAMTS1 knockout suppressed intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice, indicating its role in promoting glioma invasion likely by regulating the Notch1-SOX2 signaling pathway [1]. In renal cell carcinoma, manipulation of ADAMTS1 affected cell anoikis through the mitochondrial pathway, and in vivo knockdown of VCAN or EGFR reversed ADAMTS1-induced prometastatic characteristics, uncovering an ADAMTS1-VCAN-EGFR cyclic axis in promoting invasion and anoikis resistance [3]. In non-small cell lung cancer, overexpression of ADAMTS1 in a tumor metastasis model promoted EMT and lung metastasis, and its oncogenic effects could be reversed by inhibiting TGF-β, which ADAMTS1 positively regulates [4]. In polycystic kidney disease, deletion of both Adamts1 and Pkd1 reduced versican cleavage, macrophage accumulation, and cyst growth, improving kidney function and survival [5]. In a mouse model of ventricular noncompaction caused by a CHD4 mutation, administration of ADAMTS1 rescued hyperproliferation and hypertrabeculation defects [6].

In conclusion, ADAMTS1 is a key matrix metalloproteinase involved in multiple biological processes and disease conditions. Gene knockout and related functional studies in mouse models have significantly advanced our understanding of its role in promoting tumor invasion in glioma, renal cell carcinoma, and non-small cell lung cancer, as well as its contribution to cyst expansion in polycystic kidney disease and ventricular noncompaction. These findings provide potential therapeutic targets for these diseases.

References:

1. Wang, Shanshan, Zhang, Jin, Wang, Ke, Zhao, Yuanli, Liu, Dongying. 2022. ADAMTS1 as potential prognostic biomarker promotes malignant invasion of glioma. In International journal of clinical oncology, 28, 52-68. doi:10.1007/s10147-022-02268-9. https://pubmed.ncbi.nlm.nih.gov/36371587/

2. Iruela-Arispe, M Luisa, Carpizo, Darren, Luque, Alfonso. . ADAMTS1: a matrix metalloprotease with angioinhibitory properties. In Annals of the New York Academy of Sciences, 995, 183-90. doi:. https://pubmed.ncbi.nlm.nih.gov/12814950/

3. Wen, Yu-Ching, Lin, Yung-Wei, Ho, Kuo-Hao, Lee, Wei-Jiunn, Chien, Ming-Hsien. 2024. The oncogenic ADAMTS1-VCAN-EGFR cyclic axis drives anoikis resistance and invasion in renal cell carcinoma. In Cellular & molecular biology letters, 29, 126. doi:10.1186/s11658-024-00643-0. https://pubmed.ncbi.nlm.nih.gov/39333870/

4. Hu, Xueqian, Jiang, Chunqi, Hu, Ning, Hong, Shanyi. 2023. ADAMTS1 induces epithelial-mesenchymal transition pathway in non-small cell lung cancer by regulating TGF-β. In Aging, 15, 2097-2114. doi:10.18632/aging.204594. https://pubmed.ncbi.nlm.nih.gov/36947712/

5. Kakade, Vijayakumar R, Akman, Zafer, Motrapu, Manga, Somlo, Stefan, Cantley, Lloyd G. 2024. Adamts1 and Cyst Expansion in Polycystic Kidney Disease. In Journal of the American Society of Nephrology : JASN, 36, 559-570. doi:10.1681/ASN.0000000557. https://pubmed.ncbi.nlm.nih.gov/39514301/

6. Shi, Wei, Scialdone, Angel P, Emerson, James I, Cook, Jeanette G, Conlon, Frank L. 2023. Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1. In Circulation research, 133, 48-67. doi:10.1161/CIRCRESAHA.122.322223. https://pubmed.ncbi.nlm.nih.gov/37254794/