Premium
SATB2 augments ΔNp63α in head and neck squamous cell carcinoma
Author(s) -
Chung Jacky,
Lau Joanne,
Cheng Lynn S,
Grant R Ian,
Robinson Fiona,
Ketela Troy,
Reis Patricia P,
Roche Olga,
KamelReid Suzanne,
Moffat Jason,
Ohh Michael,
PerezOrdonez Bayardo,
Kaplan David R,
Irwin Meredith S
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.125
Subject(s) - head and neck squamous cell carcinoma , cancer research , gene knockdown , apoptosis , transcription factor , cell , biology , rna interference , gene , cancer , rna , head and neck cancer , genetics
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.