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Cell Stem Cell. 2011 Feb 4;8(2):164-76. doi: 10.1016/j.stem.2010.12.009.

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

Author information

1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. bill.keyes@crg.es

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.

PMID:
21295273
PMCID:
PMC4373450
DOI:
10.1016/j.stem.2010.12.009
[Indexed for MEDLINE]
Free PMC Article

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