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YAP drives cutaneous squamous cell carcinoma formation and progression

dc.contributor.authorVincent-Mistiaen, Zoe
dc.contributor.authorElbediwy, Ahmed
dc.contributor.authorVanyai, Hannah
dc.contributor.authorCotton, Jennifer L.
dc.contributor.authorStamp, Gordon
dc.contributor.authorNye, Emma
dc.contributor.authorSpencer-Dene, Bradley
dc.contributor.authorThomas, Gareth J.
dc.contributor.authorMao, Junhao
dc.contributor.authorThompson, Barry
dc.date2022-08-11T08:09:51.000
dc.date.accessioned2022-08-23T16:46:06Z
dc.date.available2022-08-23T16:46:06Z
dc.date.issued2018-09-20
dc.date.submitted2018-11-19
dc.identifier.citation<p>Elife. 2018 Sep 20;7. pii: 33304. doi: 10.7554/eLife.33304. <a href="https://doi.org/10.7554/eLife.33304">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.33304
dc.identifier.pmid30231971
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40813
dc.description.abstractSquamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where tumour-initiating epithelial cells undergo EMT to generate spSCC. Expression of the EMT transcription factor ZEB1 arises upon wounding and is a defining characteristic of spSCC in mice and humans. Thus, the wound healing response synergises with YAP to drive metaplastic transformation of SCC to spSCC.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30231971&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2018, Vincent-Mistiaen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHippo pathway
dc.subjectYAP
dc.subjectcarcinoma
dc.subjectdevelopmental biology
dc.subjectmouse
dc.subjectregenerative medicine
dc.subjectstem cells
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.subjectNeoplasms
dc.titleYAP drives cutaneous squamous cell carcinoma formation and progression
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4632&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3620
dc.identifier.contextkey13342666
refterms.dateFOA2022-08-23T16:46:06Z
html.description.abstract<p>Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where tumour-initiating epithelial cells undergo EMT to generate spSCC. Expression of the EMT transcription factor ZEB1 arises upon wounding and is a defining characteristic of spSCC in mice and humans. Thus, the wound healing response synergises with YAP to drive metaplastic transformation of SCC to spSCC.</p>
dc.identifier.submissionpathoapubs/3620
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.source.pagese33304


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Copyright © 2018, Vincent-Mistiaen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2018, Vincent-Mistiaen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.