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

Staquicini, Fernanda I.; Qian, Ming D.; Salameh, Ahmad; Dobroff, Andrey S.; Edwards, Julianna K.; Cimino, Daniel F.; Moeller, Benjamin J.; Kelly, Patrick; Nunez, Maria I.; Tang, Ximing; Liu, Diane D.; Lee, J. Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R. M.; Lobb, Roy R.; Edelman, Martin J.; Sidman, Richard L.; Wistuba, Ignacio I.; Arap, Wadih; Pasqualini, Renata

doi:10.1074/jbc.M114.630525

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

Journal Article · Fri Mar 20 00:00:00 EDT 2015 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M114.630525· OSTI ID:1225738

Staquicini, Fernanda I. ^[1]; Qian, Ming D. ^[2]; Salameh, Ahmad ^[2]; Dobroff, Andrey S. ^[1]; Edwards, Julianna K. ^[2]; Cimino, Daniel F. ^[1]; Moeller, Benjamin J. ^[2]; Kelly, Patrick ^[2]; Nunez, Maria I. ^[2]; Tang, Ximing ^[2]; Liu, Diane D. ^[2]; Lee, J. Jack ^[2]; Hong, Waun Ki ^[2]; Ferrara, Fortunato ^[1]; Bradbury, Andrew R. M. ^[3]; Lobb, Roy R. ^[4]; Edelman, Martin J. ^[4]; Sidman, Richard L. ^[5]; Wistuba, Ignacio I. ^[2]; Arap, Wadih ^[1] more »

Univ. of Mexico School of Medicine, Albuquerque, NM (United States)
Univ. of Texas M. D. Anderson Cancer Center, Houston, TX (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Arrowhead Research Corp., Pasadena, CA (United States)
Harvard Medical School, Boston, MA (United States)

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. In conclusion, 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.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1225738

Report Number(s):: LA-UR-14-27894

Journal Information:: Journal of Biological Chemistry, Vol. 290, Issue 12; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 37 works

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59 BASIC BIOLOGICAL SCIENCES
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receptor tyrosine kinase
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Title: Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer

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