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Morehead City, NC, United States

Staquicini F.I.,University of New Mexico | Qian M.D.,University of Texas M. D. Anderson Cancer Center | Salameh A.,University of Texas M. D. Anderson Cancer Center | Dobroff A.S.,University of New Mexico | And 19 more authors.
Journal of Biological Chemistry | Year: 2015

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015, American Society for Biochemistry and Molecular Biology Inc. All rights reserved.

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