DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma

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DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma

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Title: DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma
Author: Berger, Alice H.; Chen, Ming; Morotti, Alessandro; Janas, Justyna A.; Niki, Masaru; Bronson, Roderick T.; Taylor, Barry S.; Ladanyi, Marc; Van Aelst, Linda; Politi, Katerina; Varmus, Harold E.; Pandolfi, Pier Paolo

Note: Order does not necessarily reflect citation order of authors.

Citation: Berger, A. H., M. Chen, A. Morotti, J. A. Janas, M. Niki, R. T. Bronson, B. S. Taylor, et al. 2013. “DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma.” PLoS ONE 8 (11): e79526. doi:10.1371/journal.pone.0079526. http://dx.doi.org/10.1371/journal.pone.0079526.
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Abstract: Somatic mutations in the EGFR proto-oncogene occur in ~15% of human lung adenocarcinomas and the importance of EGFR mutations for the initiation and maintenance of lung cancer is well established from mouse models and cancer therapy trials in human lung cancer patients. Recently, we identified DOK2 as a lung adenocarcinoma tumor suppressor gene. Here we show that genomic loss of DOK2 is associated with EGFR mutations in human lung adenocarcinoma, and we hypothesized that loss of DOK2 might therefore cooperate with EGFR mutations to promote lung tumorigenesis. We tested this hypothesis using genetically engineered mouse models and find that loss of Dok2 in the mouse accelerates lung tumorigenesis initiated by oncogenic EGFR, but not that initiated by mutated Kras. Moreover, we find that DOK2 participates in a negative feedback loop that opposes mutated EGFR; EGFR mutation leads to recruitment of DOK2 to EGFR and DOK2-mediated inhibition of downstream activation of RAS. These data identify DOK2 as a tumor suppressor in EGFR-mutant lung adenocarcinoma.
Published Version: doi:10.1371/journal.pone.0079526
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821857/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879070
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