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Metastatic progression is characterised by extensive remodelling of the extracellular matrix, primarily mediated by secreted proteases, including members of the \u2018a disintegrin and metalloprotease with thrombospondin motif\u2019 (ADAMTS) family. In particular, ADAMTS5 has been reported to be upregulated in ovarian malignant tumours compared to borderline and benign lesions, suggesting it might play a role in metastatic progression. Furthermore, it has been suggested that Rab25, a small GTPase of the Ras family, might upregulate ADAMTS5 expression in ovarian cancer cells. Here we demonstrated that Rab25 promotes ADAMTS5 expression through the activation of the nuclear factor \u03baB (NF\u2010\u03baB) signalling pathway. Furthermore, ADAMTS5 was necessary and sufficient to stimulate ovarian cancer cell migration through complex fibroblast\u2010secreted matrices, while selective ADAMTS5 inhibition prevented ovarian cancer spheroid invasion in 3D systems. Finally, in ovarian cancer patients, high ADAMTS5 expression correlated with poor prognosis. Altogether, these data identify ADAMTS5 as a novel regulator of ovarian cancer cell migration and invasion, suggesting it might represent a previously undescribed therapeutic target to prevent ovarian cancer metastasis.<\/jats:p>","DOI":"10.1111\/febs.70080","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T20:43:22Z","timestamp":1743540202000},"page":"4491-4515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The protease\n                    <scp>ADAMTS<\/scp>\n                    5 controls ovarian cancer cell invasion, downstream of Rab25"],"prefix":"10.1111","volume":"292","author":[{"given":"Shengnan","family":"Yuan","sequence":"first","affiliation":[{"name":"School of Biosciences University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachele","family":"Bacchetti","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Adams","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  UK"},{"name":"Clinical Medicine, School of Medicine &amp; Population Health University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doretta","family":"Cuffaro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Rossello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-5376","authenticated-orcid":false,"given":"Elisa","family":"Nuti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Santamaria","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, School of Biosciences, Faculty of Health and Medical Sciences University of Surrey  Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-8701","authenticated-orcid":false,"given":"Elena","family":"Rainero","sequence":"additional","affiliation":[{"name":"School of Biosciences University of Sheffield  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092246"},{"key":"e_1_2_10_4_1","unstructured":"BhatlaN&JonesA(2018)The World ovarian cancer coalition atlas."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1098"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-0530-4"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18794-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0676-3"},{"key":"e_1_2_10_9_1","first-page":"1","article-title":"ADAMTS proteases: their multifaceted role in the regulation of cancer metastasis","volume":"3","author":"Bacchetti R","year":"2024","journal-title":"Dis Res"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000446244"},{"key":"e_1_2_10_11_1","unstructured":"Do\u017cynkiewiczMA(2011)The role of the chloride intracellular channel\u20103 (CLIC3) in integrin trafficking and tumour progression. 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