{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:50:15Z","timestamp":1787320215998,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tour de Cure Pioneering grant"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1127452"],"award-info":[{"award-number":["1127452"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1177837"],"award-info":[{"award-number":["1177837"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian Government Operational Infrastructure Support Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ADAM10 is a transmembrane metalloprotease that regulates diverse signalling functions via the shedding of membrane protein ectodomains, and is implicated in tumour development, including glioblastoma multiforme (GBM) and gastrointestinal (GI) cancers, where high ADAM10 expression is associated with poor prognosis. We assessed the role of ADAM10 by gene knockout (KO) in U251 GBM cells, and its effects on protein shedding and protein expression on cell proliferation and on the growth of tumour xenografts in mice. The growth of tumours was severely delayed, relative to modest effects on proliferation in vitro, suggesting roles particularly in the context of the tumour microenvironment (TME). Proteomics analysis of KO cell-conditioned medium showed decreased levels of known ADAM10 targets such as Notch and Eph receptors and ligands, as well as other proteins involved in cell\u2013cell adhesion, migration, signalling, metabolism, differentiation, and development, including angiogenesis. KO cell and tumour lysate analysis also showed modulation of proteins associated with metabolic and catalytic activity, cell\u2013matrix organisation and differentiation. Similar effects were also observed in the SW620 colon cancer model, indicating broader significance. Furthermore, expression of the associated protein sets also correlated with ADAM10 expression in human GBM and colon cancer specimens (TCGA datasets), indicating clinical relevance. Collagens and proteins associated with matrix deposition and fibril organisation were notably reduced in ADAM10 KO GBM tumours, and histology confirmed decreased collagen fibrils and blood vessels. Unexpectedly, increased chondrocyte differentiation was evident in ADAM10 KO U251 tumours, suggesting a role for ADAM10 in maintaining an undifferentiated phenotype in vivo. Together, our data indicate the importance of ADAM10 in diverse signalling mechanisms in tumours and the TME that promote tumour development.<\/jats:p>","DOI":"10.3390\/ijms262110684","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ADAM10 Knockout from Human Glioblastoma and Colon Cancer Cells Modulates Diverse Signalling Networks and Inhibits Tumour Growth In Vivo"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-2959","authenticated-orcid":false,"given":"Hengkang","family":"Yan","sequence":"first","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-9447","authenticated-orcid":false,"given":"Sakshi","family":"Arora","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hii","sequence":"additional","affiliation":[{"name":"Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Llerena","sequence":"additional","affiliation":[{"name":"Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-8940","authenticated-orcid":false,"given":"Mary E.","family":"Vail","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Allam","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R. W.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel R.","family":"Steele","sequence":"additional","affiliation":[{"name":"Proteomics & Metabolomics Platform, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-757X","authenticated-orcid":false,"given":"Han-Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Proteomics & Metabolomics Platform, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8738-1878","authenticated-orcid":false,"given":"Ralf B.","family":"Schittenhelm","sequence":"additional","affiliation":[{"name":"Proteomics & Metabolomics Platform, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Scott","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9039-1097","authenticated-orcid":false,"given":"Peter W.","family":"Janes","sequence":"additional","affiliation":[{"name":"Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia"},{"name":"School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia"},{"name":"Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.semcdb.2008.11.002","article-title":"The \u201cA Disintegrin And Metalloprotease\u201d (ADAM) family of sheddases: Physiological and cellular functions","volume":"20","author":"Reiss","year":"2009","journal-title":"Semin. 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