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

WM Keyes, M Pecoraro, V Aranda… - Cell stem cell, 2011 - cell.com
WM Keyes, M Pecoraro, V Aranda, E Vernersson-Lindahl, W Li, H Vogel, X Guo, EL Garcia…
Cell stem cell, 2011cell.com
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 …
Summary
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.
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