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Compared with epithelial carcinomas, however, the impact of fibrillar collagens on malignant mesenchymal tumours, including uterine leiomyosarcoma (uLMS), remains elusive. In this study, we analyse the network morphology and density of fibrillar collagens combined with the gene expression within uLMS, LM and normal myometrium (MM). We find that, in contrast to LM, uLMS tumours present low collagen density and increased expression of collagen\u2010remodelling genes, features associated with tumour aggressiveness. Using collagen\u2010based 3D matrices, we show that matrix metalloproteinase\u201014 (MMP14), a central protein with collagen\u2010remodelling functions that is particularly overexpressed in uLMS, supports uLMS cell proliferation. In addition, we find that, unlike MM and LM cells, uLMS proliferation and migration are less sensitive to changes in collagen substrate stiffness. We demonstrate that uLMS cell growth in low\u2010stiffness substrates is sustained by an enhanced basal yes\u2010associated protein 1 (YAP) activity. Altogether, our results indicate that uLMS cells acquire increased collagen remodelling capabilities and are adapted to grow and migrate in low collagen and soft microenvironments. These results further suggest that matrix remodelling and YAP are potential therapeutic targets for this deadly disease.<\/jats:p>","DOI":"10.1002\/1878-0261.13440","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T07:23:50Z","timestamp":1681975430000},"page":"850-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<i>MMP14<\/i>\n                    expression and collagen remodelling support uterine leiomyosarcoma aggressiveness"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-1498","authenticated-orcid":false,"given":"Jordi","family":"Gonzalez\u2010Molina","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Oncology\u2010Pathology Karolinska Institutet  Stockholm 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