{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADAMTS15 is a multifunctional secreted metalloproteinase that plays diverse roles in extracellular matrix (ECM) remodeling, development, and cancer suppression. Expression studies in the brain reveal that ADAMTS15 is selectively expressed by parvalbumin‐expressing interneurons where it is thought to participate in the dynamic remodeling of the perineuronal net (PNN)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the developing embryo, ADAMTS15 is processed by furin to generate an active enzyme capable of cleaving the proteoglycan versican at a specific E↓A bond – a key step in reshaping versican‐rich matrices in tissues such as the heart, musculoskeletal system, and colon."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, during skeletal myogenesis, ADAMTS15 cooperates with related proteases to remodel the pericellular matrix and promote myoblast fusion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, ADAMTS15 displays tumor‐suppressive activities. For example, higher ADAMTS15 expression is linked to prolonged relapse‐free survival in breast cancer patients"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and its genetic inactivation in colorectal cancer correlates with enhanced tumor growth and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Complementary in vitro and in vivo studies in breast cancer models further indicate that the catalytic activity of ADAMTS15 is necessary to inhibit cell migration and angiogenesis, with its effects on metastasis being dependent on the specific tissue context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, a low‐frequency variant in ADAMTS15 associated with familial intracranial aneurysms suggests that disruption of its function may accelerate endothelial cell migration, thereby affecting angiogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, clinical studies report that ADAMTS15 is also upregulated in leiomyomas—potentially contributing to altered ECM turnover in smooth muscle tissues"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "—and its expression in prostate cancer appears to be regulated by androgen signaling, underscoring its potential as a prognostic marker in this context."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings position ADAMTS15 as a critical modulator of ECM integrity with important roles in developmental morphogenesis, myogenesis, and the suppression of tumor progression via regulation of cell–matrix interactions and angiogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Rossier, A Bernard, J-H Cabungcal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2014.162"}], "href": "https://doi.org/10.1038/mp.2014.162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25510509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25510509"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carolyn M Dancevic, Fiona W Fraser, Adam D Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biosynthesis and expression of a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats-15: a novel versican-cleaving proteoglycanase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.418624"}], "href": "https://doi.org/10.1074/jbc.M112.418624"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24220035"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24220035"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicole Stupka, Christopher Kintakas, Jason D White, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.429647"}], "href": "https://doi.org/10.1074/jbc.M112.429647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23233679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23233679"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sarah Porter, Paul N Span, Fred C G J Sweep, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.21476"}], "href": "https://doi.org/10.1002/ijc.21476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16152618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16152618"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Cristina G Viloria, Alvaro J Obaya, Angela Moncada-Pazos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic inactivation of ADAMTS15 metalloprotease in human colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-4155"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-4155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19458070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19458070"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Richard Kelwick, Laura Wagstaff, Julie Decock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metalloproteinase-dependent and -independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs-15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.29129"}], "href": "https://doi.org/10.1002/ijc.29129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25099234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25099234"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Junxia Yan, Toshiaki Hitomi, Katsunobu Takenaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic study of intracranial aneurysms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.114.007286"}], "href": "https://doi.org/10.1161/STROKEAHA.114.007286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25649796"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25649796"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ndeye-Aicha Gueye, Timothy J Mead, Christopher D Koch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Versican Proteolysis by ADAMTS Proteases and Its Influence on Sex Steroid Receptor Expression in Uterine Leiomyoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2016-3527"}], "href": "https://doi.org/10.1210/jc.2016-3527"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28323982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28323982"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chidi N Molokwu, Olajumoke O Adeniji, Shankar Chandrasekharan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Androgen regulates ADAMTS15 gene expression in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Invest (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/07357907.2010.489538"}], "href": "https://doi.org/10.3109/07357907.2010.489538"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20590445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20590445"}]}]}]}