SATB2 augments [Delta]Np63[alpha] in head and neck squamous cell carcinoma

ΔNp63α is a critical pro-survival protein overexpressed in 80% of head and neck squamous cell carcinomas (HNSCCs) where it inhibits TAp73β transcription of p53-family target genes, which is thought to increase HNSCC resistance to chemotherapy-induced cell death. However, the mechanisms governing ΔNp...

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Bibliographic Details
Published in:EMBO reports 2010-10, Vol.11 (10), p.777
Main Authors: Chung, Jacky, Lau, Joanne, Cheng, Lynn S, Grant, R Ian, Robinson, Fiona, Ketela, Troy, Reis, Patricia P, Roche, Olga, Kamel-reid, Suzanne, Moffat, Jason, Ohh, Michael, Perez-ordonez, Bayardo, Kaplan, David R, Irwin, Meredith S
Format: Article
Language:English
Subjects:
Cells
Chemotherapy
Head & neck cancer
Irradiation
Survival
Tumors
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Summary:ΔNp63α is a critical pro-survival protein overexpressed in 80% of head and neck squamous cell carcinomas (HNSCCs) where it inhibits TAp73β transcription of p53-family target genes, which is thought to increase HNSCC resistance to chemotherapy-induced cell death. However, the mechanisms governing ΔNp63α function are largely unknown. In this study, we identify special AT-rich-binding protein 2 (SATB2) as a new ΔNp63α-binding protein that is preferentially expressed in advanced-stage primary HNSCC and show that SATB2 promotes chemoresistance by enhancing ΔNp63α-mediated transrepression by augmenting ΔNp63α engagement to p53-family responsive elements. Furthermore, SATB2 expression positively correlates with HNSCC chemoresistance, and RNA interference-mediated knockdown of endogenous SATB2 re-sensitizes HNSCC cells to chemotherapy- and γ-irradiation-induced apoptosis, irrespective of p53 status. These findings unveil SATB2 as a pivotal modulator of ΔNp63α that governs HNSCC cell survival..[PUBLICATION ABSTRACT]
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2010.125