{"doi":"10.1371/journal.pone.0079526","title":"DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma","abstract":null,"journal":"PLoS ONE","year":2013,"id":618056,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":588975,"name":"Ming Chen","orcid":"0000-0003-2570-0858","position":1,"is_corresponding":false},{"id":1594190,"name":"Alessandro Morotti","orcid":null,"position":2,"is_corresponding":false},{"id":684536,"name":"Justyna A. Janas","orcid":"0000-0001-9840-9928","position":3,"is_corresponding":false},{"id":1508172,"name":"Masaru Niki","orcid":null,"position":4,"is_corresponding":false},{"id":39878,"name":"Roderick T. Bronson","orcid":"0000-0003-3725-2511","position":5,"is_corresponding":false},{"id":1862,"name":"Barry S. Taylor","orcid":"0000-0002-3355-9471","position":6,"is_corresponding":false},{"id":1869,"name":"Marc Ladanyi","orcid":"0000-0001-9055-7213","position":7,"is_corresponding":false},{"id":322312,"name":"Linda Van Aelst","orcid":"0000-0002-0870-012X","position":8,"is_corresponding":false},{"id":1261,"name":"Katerina Politi","orcid":"0000-0001-6064-4527","position":9,"is_corresponding":false},{"id":1594194,"name":"Harold E. Varmus","orcid":null,"position":10,"is_corresponding":false},{"id":23892,"name":"Pier Paolo Pandolfi","orcid":"0000-0002-5352-5295","position":11,"is_corresponding":false},{"id":79456,"name":"Alice H. Berger","orcid":"0000-0002-6538-2658","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"DOK2 Inhibits EGFR-Mutated Lung Adenocarcinoma","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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24255704","pmcid":"PMC3821857","openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R00 CA131488","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA142787","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA-142787","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA-131488","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01 CA129243","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA120247","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA-120247","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA-129243","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K99 CA131488","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01CA142787-03","title":"Role of DOK family proteins in lung tumor suppression"},{"funder_name":"National Institutes of Health","grant_id":"5P01CA129243-07","title":"Mechanisms and Modulators of Sensitivity and Resistance to EGFR Inhibitors in Lu"},{"funder_name":"National Institutes of Health","grant_id":"5R01CA120247-09","title":"Mutant EGF Receptor-Dependent Lung Cancer in Human Cell Lines and Transgenic Mice"}],"total_grants":12,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0079526&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0079526","host_type":"publisher"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879070","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3821857","host_type":"repository"},{"url":"http://hdl.handle.net/2318/148879","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3821857","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3821857?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pone.0079526","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/24255704","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pone.0079526","host_type":""},{"url":"https://doaj.org/article/cab9c345823b4a82ad45b38dba310350","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0079526","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pone.0079526","host_type":""}],"fields_of_study":["0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Cell Line","Animals","Mice, Transgenic","Humans","Mice","Adenocarcinoma","Lung Neoplasms","Epidermal Growth Factor","ras Proteins","Extracellular Signal-Regulated MAP Kinases","Adaptor Proteins, Signal Transducing","Tumor Suppressor Proteins","Phosphoproteins","Genomics","Mutation","Male","Gene Knockout Techniques","Carcinogenesis","ErbB Receptors","Adenocarcinoma of Lung","Proto-Oncogene Mas"],"keywords":["Male","Lung Neoplasms","Carcinogenesis","Science","610","Adenocarcinoma of Lung","Mice, Transgenic","Adenocarcinoma","Proto-Oncogene Mas","Transgenic","Cell Line","Gene Knockout Techniques","Mice","616","Animals","Humans","Extracellular Signal-Regulated MAP Kinases","Adaptor Proteins, Signal Transducing","Epidermal Growth Factor","Tumor Suppressor Proteins","Q","Signal Transducing","R","Adaptor Proteins","Genomics","Phosphoproteins","ErbB Receptors","Mutation","ras Proteins","Medicine","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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