Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

Autor:	Staquicini FI; From the University of New Mexico Cancer Center and the Divisions of Molecular Medicine and., Qian MD; the Departments of Genitourinary Medical Oncology., Salameh A; the Departments of Genitourinary Medical Oncology., Dobroff AS; From the University of New Mexico Cancer Center and the Divisions of Molecular Medicine and., Edwards JK; the Departments of Genitourinary Medical Oncology., Cimino DF; From the University of New Mexico Cancer Center and the Divisions of Molecular Medicine and., Moeller BJ; the Departments of Genitourinary Medical Oncology, Radiation Oncology., Kelly P; the Departments of Genitourinary Medical Oncology, Radiation Oncology., Nunez MI; Translational Molecular Pathology., Tang X; Translational Molecular Pathology., Liu DD; Biostatistics, and., Lee JJ; Biostatistics, and., Hong WK; Thoracic/Head & Neck Medical Oncology, David H. Koch Center, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030., Ferrara F; From the University of New Mexico Cancer Center and the Divisions of Molecular Medicine and., Bradbury AR; the Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545., Lobb RR; Alvos Therapeutics, Arrowhead Research Corporation, Pasadena, California 91101., Edelman MJ; Alvos Therapeutics, Arrowhead Research Corporation, Pasadena, California 91101., Sidman RL; the Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215., Wistuba II; Translational Molecular Pathology., Arap W; From the University of New Mexico Cancer Center and Hematology/Medical Oncology, Department of Internal Medicine University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-0001, warap@salud.unm.edu., Pasqualini R; From the University of New Mexico Cancer Center and the Divisions of Molecular Medicine and rpasqual@salud.unm.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2015 Mar 20; Vol. 290 (12), pp. 7345-59. Date of Electronic Publication: 2015 Jan 26.
DOI:	10.1074/jbc.M114.630525
Abstrakt:	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 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu