SATB2 augments ΔNp63α in head and neck squamous cell carcinoma

EMBO Rep. 2010 Oct;11(10):777-83. doi: 10.1038/embor.2010.125. Epub 2010 Sep 10.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Cell Survival
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic*
  • Genes, p53
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • DNA-Binding Proteins
  • Matrix Attachment Region Binding Proteins
  • SATB2 protein, human
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins