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)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jan 7 2011|
Bibliographical noteFunding 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.