{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:14:33Z","timestamp":1784258073366,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,9]],"date-time":"2013-10-09T00:00:00Z","timestamp":1381276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"Abstract<\/jats:title>Deregulated NOTCH1<\/jats:styled-content> has been reported in lymphoid leukaemia, although its role in chronic myeloid leukaemia (CML<\/jats:styled-content>) is not well established. We previously reported BCR\u2010ABL<\/jats:styled-content> down\u2010regulation of a novel haematopoietic regulator, CCN3<\/jats:styled-content>, in CML<\/jats:styled-content>; CCN3<\/jats:styled-content> is a non\u2010canonical NOTCH1<\/jats:styled-content> ligand. This study characterizes the NOTCH1\u2013CCN3<\/jats:styled-content> signalling axis in CML<\/jats:styled-content>. In K562<\/jats:styled-content> cells, BCR\u2010ABL<\/jats:styled-content><\/jats:italic> silencing reduced full\u2010length NOTCH1<\/jats:styled-content> (NOTCH1\u2010FL<\/jats:styled-content>) and inhibited the cleavage of NOTCH1<\/jats:styled-content> intracellular domain (NOTCH1\u2010ICD<\/jats:styled-content>), resulting in decreased expression of the NOTCH1<\/jats:styled-content> targets c\u2010MYC<\/jats:styled-content> and HES1<\/jats:styled-content>. K562<\/jats:styled-content> cells stably overexpressing CCN3<\/jats:styled-content> (K562<\/jats:styled-content>\/CCN3<\/jats:styled-content>) or treated with recombinant CCN3<\/jats:styled-content> (rCCN3<\/jats:styled-content>) showed a significant reduction in NOTCH1<\/jats:styled-content> signalling (> 50% reduction in NOTCH1\u2010ICD<\/jats:styled-content>, p<\/jats:italic> < 0.05). Gamma secretase inhibitor (GSI<\/jats:styled-content>), which blocks NOTCH1<\/jats:styled-content> signalling, reduced K562<\/jats:styled-content>\/CCN3<\/jats:styled-content> colony formation but increased that of K562<\/jats:styled-content>\/control cells. GSI<\/jats:styled-content> combined with either rCCN3<\/jats:styled-content> or imatinib reduced K562<\/jats:styled-content> colony formation with enhanced reduction of NOTCH1<\/jats:styled-content> signalling observed with combination treatments. We demonstrate an oncogenic role for NOTCH1<\/jats:styled-content> in CML<\/jats:styled-content> and suggest that BCR\u2010ABL<\/jats:styled-content> disruption of NOTCH1\u2013CCN3<\/jats:styled-content> signalling contributes to the pathogenesis of CML<\/jats:styled-content>. \u00a9 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4246","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T06:50:43Z","timestamp":1376290243000},"page":"378-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The matricellular protein CCN3<\/scp> regulates NOTCH1<\/scp> signalling in chronic myeloid leukaemia"],"prefix":"10.1002","volume":"231","author":[{"given":"Sukanya","family":"Suresh","sequence":"first","affiliation":[{"name":"Centre for Cancer Research and Cell Biology Queen's University Lisburn Road Belfast BT9 7BL UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"McCallum","sequence":"additional","affiliation":[{"name":"School of Biomedical and Biological Sciences, Portland Square University of Plymouth Drake Circus 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