Anti-EGFR function of EFEMP1 in glioma cells and patient prognosis
Yuanjie Hu1, Hengjun Gao2,3, Christopher Vo4, Chao Ke4,5, Francine Pan4, Liping Yu6, Eric Siegel7, Kenneth R. Hess8, Mark E. Linskey4, Yi-Hong Zhou1,4
1 Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA
2 Institute of Digestive Disease, Tongji University, Shanghai, China
3 National Engineering Center for Biochip at Shanghai, Shanghai, China
4 Neurological Surgery, University of California Irvine, Irvine, CA, USA
5 State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
6 Ziren Research LLC, Irvine, CA, USA
7 Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
8 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence:
Yi-Hong Zhou, email:
Keywords: EFEMP1, EGFR, glioma, prognosis, tumorigenicity
Received: January 30, 2014 Accepted: March 24, 2014 Published: March 25, 2014
Abstract
EGFR is one of the key oncogenes subjected to targeted therapy for several cancers, as it is known to be amplified and/or mutated in up to 40% of malignant gliomas. EFEMP1, a fibulin-like extracellular protein, exerts both tumor suppressive and oncogenic effects in various cancers and glioma cell models. Although EFEMP1’s anti-cancer activity has most commonly been attributed to its anti-angiogenic effects, we showed for gliomas that EFEMP1’s binding to EGFR accounts for its suppression of the intracranial tumorigenicity of glioma cells expressing high levels of EGFR. In gliomas where EFEMP1 expression, and thus the anti-EGFR effect of EFEMP1, was suppressed, heightened levels of EGFR expression were associated with unfavorable patient outcomes in prognostic models. Results from the current study clearly demonstrate the impact that the anti-EGFR function of EFEMP1 has on the expression of EGFR and patient prognosis. A glioma prognostic model also suggests EFEMP1’s context-dependent oncogenic function in gliomas expressing low levels of EGFR. Hence the level of EFEMP1 expression may have a predictive value for choosing patients for anti-EGFR therapy.
