ΔNp63α is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis

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• dc.contributor.author Keyes, William M., 1973-
• dc.contributor.author Pecoraro, Matteo, 1984-
• dc.contributor.author Aranda, Victoria
• dc.contributor.author Vernersson Lindahl, Emma
• dc.contributor.author Li, Wangzhi
• dc.contributor.author Vogel, Hannes
• dc.contributor.author Guo, Xuecui
• dc.contributor.author Garcia, Elvin L.
• dc.contributor.author Michurina, Tatyana V.
• dc.contributor.author Enikolopov, Grigori
• dc.contributor.author Muthuswamy, Senthil K.
• dc.contributor.author Mills, Alea A.
• dc.date.accessioned 2020-12-01T08:02:50Z
• dc.date.available 2020-12-01T08:02:50Z
• dc.date.issued 2011
• dc.description.abstract The p53 homolog p63 is essential for development, yet its role in cancer is not clear. We discovered that p63 deficiency evokes the tumor-suppressive mechanism of cellular senescence, causing a striking absence of stratified epithelia such as the skin. Here we identify the predominant p63 isoform, ΔNp63α, as a protein that bypasses oncogene-induced senescence to drive tumorigenesis in vivo. Interestingly, bypass of senescence promotes stem-like proliferation and maintains survival of the keratin 15-positive stem cell population. Furthermore, we identify the chromatin-remodeling protein Lsh as a new target of ΔNp63α that is an essential mediator of senescence bypass. These findings indicate that ΔNp63α is an oncogene that cooperates with Ras to promote tumor-initiating stem-like proliferation and suggest that Lsh-mediated chromatin-remodeling events are critical to this process.
• dc.description.sponsorship We thank Johannes Zuber, Michael Hemann, and Scott Lowe for assistance and advice; Yuri Lazebnik and Dominik Duelli for DMBA-treated tissues; Chris Johns and Sohail Khan for microarray analysis; and Leif Ellisen and James W. Rocco for HNSCC cell lines. W.M.K. was funded by the Spanish Ministry of Science and Innovation (Plan Nacional –SAF2010-18829). A.A.M. was funded by an ACS Research Scholar Award (RSG-06-190-01-MGO).
• dc.format.mimetype application/pdf
• dc.identifier.citation Keyes WM, Pecoraro M, Aranda V, Vernersson-Lindahl E, Li W, Vogel H, Guo X, Garcia EL, Michurina TV, Enikolopov G, Muthuswamy SK, Mills AA. ΔNp63α is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis. Cell Stem Cell. 2011; 8(2):164-76. DOI: 10.1016/j.stem.2010.12.009
• dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2010.12.009
• dc.identifier.issn 1934-5909
• dc.identifier.uri http://hdl.handle.net/10230/45916
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Stem Cell. 2011; 8(2):164-76
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-18829
• dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.stem.2010.12.009 that appeared in the journal Cell stem cell. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://www.elsevier.com/open-access/userlicense/1.0/
• dc.title ΔNp63α is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion