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Biochem Biophys Res Commun. 2011 Jan 7;404(1):68-73. doi: 10.1016/j.bbrc.2010.11.064. Epub 2010 Nov 19.

Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors.

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1
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Abstract

Alteration of epidermal growth factor receptor (EGFR) is involved in various human cancers and has been intensively investigated. A plethora of evidence demonstrates that posttranslational modifications of EGFR play a pivotal role in controlling its function and metabolism. Here, we show that EGFR can be acetylated by CREB binding protein (CBP) acetyltransferase. Interestingly, EGFR acetylation affects its tyrosine phosphorylation, which may contribute to cancer cell resistance to histone deacetylase inhibitors (HDACIs). Since there is an increasing interest in using HDACIs to treat various cancers in the clinic, our current study provides insights and rationale for selecting effective therapeutic regimen. Consistent with the previous reports, we also show that HDACI combined with EGFR inhibitors achieves better therapeutic outcomes and provides a molecular rationale for the enhanced effect of combination therapy. Our results unveil a critical role of EGFR acetylation that regulates EGFR function, which may have an important clinical implication.

PMID:
21094134
PMCID:
PMC3049249
DOI:
10.1016/j.bbrc.2010.11.064
[Indexed for MEDLINE]
Free PMC Article

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