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

Hui Song; Chia Wei Li; Adam M. Labaff; Seung Oe Lim; Long Yuan Li; Shu Fen Kan; Yue Chen; Kai Zhang; Jingyu Lang; Xiaoming Xie; Yan Wang; Long Fei Huo; Sheng Chieh Hsu; Xiaomin Chen; Yingming Zhao; Mien Chie Hung

doi:10.1016/j.bbrc.2010.11.064

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

Hui Song, Chia Wei Li, Adam M. Labaff, Seung Oe Lim, Long Yuan Li, Shu Fen Kan, Yue Chen, Kai Zhang, Jingyu Lang, Xiaoming Xie, Yan Wang, Long Fei Huo, Sheng Chieh Hsu, Xiaomin Chen, Yingming Zhao, Mien Chie Hung

Biochemistry, Molecular Biology, and Biophysics (CBS)

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	68-73
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	404
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2010.11.064
State	Published - Jan 7 2011

Bibliographical note

Funding Information:
We thank Drs. Stephanie A. Miller and Jennifer L. Hsu for proofreading the manuscript. We are grateful to Su Zhang and Drs. Zhenbo Han, Hirohito Yamaguchi, Ming-Chuan Hsu, and Chi-Hong Chao for technical assistance. We also thank Drs. E.Y. Chin (Brown University) and T.P. Yao (Duke University) for generously supplying the expression plasmids for p300, CBP, and PCAF. This work was supported in part by NIH CA1109311 and CA099031 (to M.-C.H.), and CA126832 (to Y.Z.); the Breast Cancer SPORE CA116199 and CCSG CA16672; Patel Memorial Breast Cancer Research Fund (to M.-C.H.); NSC97-3111-B-039 and NSC98-3111-B-039 (to M.-C.H and L.-Y.L.); NHRI-EX98-9603BC; DOH97-TD-I-111-TM003, DOH98-TD-I-111-TM002 (to L.-Y.L.); DOH97-TD-G-111-027 (to M.-C.H); DOH99-TD-C-111-005 and NSC99-2632-B-039-001-MY3 (to L.-Y.L and M.-C.H); the MD Anderson Cancer Center-China Medical University and Hospital Sister Institution Fund; and Kadoorie Charitable Foundations (to M.-C.H.). H.S. was a recipient of the NIH-NRSA Award (1UL1RR024148). In memoriam, Tiong Loi Ang for his courageous fight against cancer.

Keywords

Acetylation
CBP
EGFR
Phosphorylation
SAHA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Song, H., Li, C. W., Labaff, A. M., Lim, S. O., Li, L. Y., Kan, S. F., Chen, Y., Zhang, K., Lang, J., Xie, X., Wang, Y., Huo, L. F., Hsu, S. C., Chen, X., Zhao, Y., & Hung, M. C. (2011). Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors. Biochemical and Biophysical Research Communications, 404(1), 68-73. https://doi.org/10.1016/j.bbrc.2010.11.064

Song, H, Li, CW, Labaff, AM, Lim, SO, Li, LY, Kan, SF, Chen, Y, Zhang, K, Lang, J, Xie, X, Wang, Y, Huo, LF, Hsu, SC, Chen, X, Zhao, Y & Hung, MC 2011, 'Acetylation of EGF receptor contributes to tumor cell resistance to histone deacetylase inhibitors', Biochemical and Biophysical Research Communications, vol. 404, no. 1, pp. 68-73. https://doi.org/10.1016/j.bbrc.2010.11.064

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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.",

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note = "Funding Information: We thank Drs. Stephanie A. Miller and Jennifer L. Hsu for proofreading the manuscript. We are grateful to Su Zhang and Drs. Zhenbo Han, Hirohito Yamaguchi, Ming-Chuan Hsu, and Chi-Hong Chao for technical assistance. We also thank Drs. E.Y. Chin (Brown University) and T.P. Yao (Duke University) for generously supplying the expression plasmids for p300, CBP, and PCAF. This work was supported in part by NIH CA1109311 and CA099031 (to M.-C.H.), and CA126832 (to Y.Z.); the Breast Cancer SPORE CA116199 and CCSG CA16672; Patel Memorial Breast Cancer Research Fund (to M.-C.H.); NSC97-3111-B-039 and NSC98-3111-B-039 (to M.-C.H and L.-Y.L.); NHRI-EX98-9603BC; DOH97-TD-I-111-TM003, DOH98-TD-I-111-TM002 (to L.-Y.L.); DOH97-TD-G-111-027 (to M.-C.H); DOH99-TD-C-111-005 and NSC99-2632-B-039-001-MY3 (to L.-Y.L and M.-C.H); the MD Anderson Cancer Center-China Medical University and Hospital Sister Institution Fund; and Kadoorie Charitable Foundations (to M.-C.H.). H.S. was a recipient of the NIH-NRSA Award (1UL1RR024148). In memoriam, Tiong Loi Ang for his courageous fight against cancer. ",

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

Abstract

Bibliographical note

Keywords

UN SDGs

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