SATB2 augments ?Np63? in head and neck squamous cell carcinoma.

ABSTRACT: ?Np63? is a critical pro-survival protein overexpressed in 80% of head and neck squamous cell carcinomas (HNSCCs) where it inhibits TAp73? transcription of p53-family target genes, which is thought to increase HNSCC resistance to chemotherapy-induced cell death. However, the mechanisms governing ?Np63? function are largely unknown. In this study, we identify special AT-rich-binding protein 2 (SATB2) as a new ?Np63?-binding protein that is preferentially expressed in advanced-stage primary HNSCC and show that SATB2 promotes chemoresistance by enhancing ?Np63?-mediated transrepression by augmenting ?Np63? 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 ?-irradiation-induced apoptosis, irrespective of p53 status. These findings unveil SATB2 as a pivotal modulator of ?Np63? that governs HNSCC cell survival.

SUBMITTER: Chung J 

PROVIDER: S-EPMC2948183 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature