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These changes in biomechanical properties contribute to cancer progression by facilitating cell movement through physically constraining environments. To identify properties that enabled passage through physical constraints, cells that were more efficient at moving through narrow membrane micropores were selected from established cell lines. By examining micropore-selected human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, membrane fluidity and nuclear elasticity were excluded as primary contributors. Instead, reduced actin cytoskeleton anisotropy, focal adhesion density and cell stiffness were characteristics associated with efficient passage through constraints. By comparing transcriptomic profiles between the parental and selected populations, increased Ras\/MAPK signalling was linked with cytoskeleton rearrangements and cell softening. MEK inhibitor treatment reversed the transcriptional, cytoskeleton, focal adhesion and elasticity changes. Conversely, expression of oncogenic KRas in parental MDA MB 231 cells, or oncogenic BRaf in parental MDA MB 435 cells, significantly reduced cell stiffness. These results reveal that MAPK signalling, in addition to tumour cell proliferation, has a significant role in regulating cell biomechanics.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.224071","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T09:49:05Z","timestamp":1559296145000},"source":"Crossref","is-referenced-by-count":49,"title":["Migration through physical constraints is enabled by MAPK-induced cell softening via actin cytoskeleton re-organization"],"prefix":"10.1242","volume":"132","author":[{"given":"Dominika A.","family":"Rudzka","sequence":"first","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Spennati","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Glasgow 2 , Glasgow G12 8QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"McGarry","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hua","family":"Chim","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Glasgow 2 , Glasgow G12 8QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Neilson","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Ptak","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June","family":"Munro","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Kalna","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hedley","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Moralli","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford 3 , Roosevelt Drive, Oxford OX3 7BN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Green","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford 3 , Roosevelt Drive, Oxford OX3 7BN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mason","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Blyth","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Mullin","sequence":"additional","affiliation":[{"name":"University of Glasgow 4 Electron Microscopy Facility, Department of Chemistry , , Glasgow G12 8QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabing","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Engineering, University of Glasgow 2 , Glasgow G12 8QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-3507","authenticated-orcid":false,"given":"Michael F.","family":"Olson","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute 1 , Garscube Estate, Switchback Road, Glasgow G61 1BD , UK"},{"name":"Institute of Cancer Sciences, University of Glasgow 5 , Glasgow G12 8QQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"2024061318150490800_JCS224071C1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/boc.201600078","article-title":"Are cancer cells really softer than normal cells?","volume":"109","author":"Alibert","year":"2017","journal-title":"Biol. 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