
-   ADAMTS1 has angioinhibitory effects in primary gastric cancer due to its low expression and negative correlation with VEGF and microvessel density (MVD) [PMID: 23001403]. ADAMTS1 was shown to have angioinhibitory properties. ADAMTS1 influences pro-angiogenic signaling events and inhibits endothelial cell proliferation by binding to VEGF and inhibiting VEGFR2 phosphorylation [PMID: 12814950]. The effect on VEGFR2 function was due to direct binding and sequestration of VEGF165 by ADAMTS1[PMID: 12716911].
-   Contribution of ADAMTS1 as a tumor suppressor in human breast carcinoma was linked to its proteolytic activity on nidogen-1 and -2 [PMID: 23681936].
-   ADAMTS1 deficiency attenuated beta-aminopropionitrile-dependent thoracic aortic aneurysm and dissection formation and rupture. ADAMTS1 deficiency suppressed neutrophil and macrophage infiltration by inhibiting inflammatory cytokine levels and macrophage migration during the early stage of beta-aminopropionitrile-induced thoracic aortic aneurysms and dissections [PMID: 30191627].
-   As ADAMTS1 promoter hypermethylation occurs during prostate cancer development, epigenetic gene expression changes induced by TGF-beta and/or AR may underpin the downregulation of ADAMTS1 with increasing castrate resistance in prostate cancer [PMID: 23444028].
-   As an ECM degrading protease, ADAMTS1 imposes its pro-metastatic effects indirectly by cleaving its substrates in the ECM (e.g., versican, syndecan-4, aggrecan) and liberating cancer cells from the structural barriers they adhere to [PMID: 20592310, PMID: 18775505, PMID: 10930576].

## Summary

The ADAMTS1 protein is involved in the degradation of extracellular matrix (ECM) components like versican, aggrecan, and syndecan-4, which are critical for maintaining the structural integrity of tissues [CS: 9]. By enhancing the breakdown of ECM components, ADAMTS1 facilitates the removal of damaged ECM and aids in the remodeling process. This action is critical for clearing away damaged tissue and making way for new cell growth and tissue repair [CS: 8]. In the context of intestinal inflammation or cancer, however, the overexpression of ADAMTS1 and excessive breakdown of ECM components can facilitate tumor cell detachment and migration, contributing to cancer progression and metastasis [CS: 7].

Additionally, ADAMTS1's role in angiogenesis is significant [CS: 8]. Normally, ADAMTS1 inhibits angiogenesis by binding to VEGF, a key factor in the formation of new blood vessels, and preventing its interaction with the VEGF receptor [CS: 7]. Timely upregulation of ADAMTS1 regulation ensures that the angiogenic response is balanced and targeted, preventing excessive or insufficient blood vessel formation, both of which can be detrimental [CS: 6]. However, prolonged dysregulation of ADAMTS1 leads to altered angiogenic activity [CS: 7]. If ADAMTS1 is underexpressed, it could result in uncontrolled angiogenesis, providing tumors with the necessary blood supply for growth and furthering disease progression [CS: 7]. Conversely, overexpression might suppress necessary angiogenesis in healthy tissue repair processes, impeding recovery from intestinal damage [CS: 7].
