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Cancer Cell. 2006 Jan;9(1):45-56.

p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis.

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1
Massachusetts General Hospital Center for Cancer Research and Harvard Medical School, Boston, Massachusetts 02114, USA.

Abstract

We demonstrate that deltaNp63alpha is an essential survival factor in head and neck squamous cell carcinoma (HNSCC) through its ability to suppress p73-dependent apoptosis. Inhibition of endogenous p63 expression by RNAi induces apoptosis selectively in HNSCC cells that overexpress deltaNp63alpha. Knockdown of p63 induces the proapoptotic bcl-2 family members Puma and Noxa, and both their induction and subsequent cell death are p53 independent but require transactivating isoforms of p73. Inhibition of p73-dependent transcription by deltaNp63alpha involves both direct promoter binding and physical interaction with p73. In HNSCC cells lacking endogenous deltaNp63alpha expression, bcl-2 is instead upregulated and can suppress p73-mediated death. Together, these data define a pathway whereby deltaNp63alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program.

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PMID:
16413471
DOI:
10.1016/j.ccr.2005.12.013
[Indexed for MEDLINE]
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