title: Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors.
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.
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Li
authors.forename: Adam M
authors.initials: AM
authors.lastname: Labaff
authors.forename: Seung-Oe
authors.initials: SO
authors.lastname: Lim
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Kan
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Jingyu
authors.initials: J
authors.lastname: Lang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Long-Fei
authors.initials: LF
authors.lastname: Huo
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Hsu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D034741:RNA, Small Interfering / Q000235:genetics; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D034741:RNA, Small Interfering; D000077337:Vorinostat; D066246:ErbB Receptors; D008239:Lysine