{"id":"https://openalex.org/W2087257002","doi":"https://doi.org/10.1073/pnas.1105369108","title":"FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-\u03baB","display_name":"FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-\u03baB","publication_year":2011,"publication_date":"2011-04-25","ids":{"openalex":"https://openalex.org/W2087257002","doi":"https://doi.org/10.1073/pnas.1105369108","mag":"2087257002","pmid":"https://pubmed.ncbi.nlm.nih.gov/21518868","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/3093511"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.1105369108","doi":"https://doi.org/10.1073/pnas.1105369108","is_oa":false,"landing_page_url":"https://doi.org/10.1073/pnas.1105369108","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3093511","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100925272","display_name":"Canhui Guo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1316902750","display_name":"Cleveland Clinic","ror":"https://ror.org/03xjacd83","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750"]},{"id":"https://openalex.org/I4405287411","display_name":"Cleveland Clinic Research","ror":"https://ror.org/053229s83","country_code":"US","type":"facility","lineage":["https://openalex.org/I1316902750","https://openalex.org/I4405287411"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Canhui Guo","raw_affiliation_strings":["Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195","Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195","institution_ids":["https://openalex.org/I1316902750","https://openalex.org/I4405287411"]},{"raw_affiliation_string":"Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA","institution_ids":["https://openalex.org/I1316902750","https://openalex.org/I4405287411"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5080998429","display_name":"George Robert Stark","orcid":"https://orcid.org/0000-0002-8776-9597","observed_orcids":["https://orcid.org/0000-0002-8776-9597"]},"institutions":[{"id":"https://openalex.org/I1316902750","display_name":"Cleveland Clinic","ror":"https://ror.org/03xjacd83","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750"]},{"id":"https://openalex.org/I4390039247","display_name":"Case Comprehensive Cancer Center","ror":"https://ror.org/00fpjq451","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039247","https://openalex.org/I58956616"]},{"id":"https://openalex.org/I4405287411","display_name":"Cleveland Clinic Research","ror":"https://ror.org/053229s83","country_code":"US","type":"facility","lineage":["https://openalex.org/I1316902750","https://openalex.org/I4405287411"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"George R. Stark","raw_affiliation_strings":["Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195","Case Comprehensive Cancer Center"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195","institution_ids":["https://openalex.org/I1316902750","https://openalex.org/I4405287411"]},{"raw_affiliation_string":"Case Comprehensive Cancer Center","institution_ids":["https://openalex.org/I4390039247"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.855,"has_fulltext":false,"cited_by_count":46,"citation_normalized_percentile":{"value":0.73271341,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":98},"biblio":{"volume":"108","issue":"19","first_page":"7968","last_page":"7973"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11591","display_name":"NF-\u03baB Signaling Pathways","score":0.9810000061988831,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11591","display_name":"NF-\u03baB Signaling Pathways","score":0.9810000061988831,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12356","display_name":"Bioactive Compounds and Antitumor Agents","score":0.002199999988079071,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.002199999988079071,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/fer-tyrosine-kinase","display_name":"Fer tyrosine kinase","score":0.9810000061988831},{"id":"https://openalex.org/keywords/quinacrine","display_name":"quinacrine","score":0.9350000023841858},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.9800000190734863},{"id":"https://openalex.org/keywords/nf-kappab-activation","display_name":"NF-\u03baB activation","score":0.9890000224113464},{"id":"https://openalex.org/keywords/egf-receptor","display_name":"EGF receptor","score":0.8289999961853027},{"id":"https://openalex.org/keywords/egfr","display_name":"EGFR","score":0.5910000205039978},{"id":"https://openalex.org/keywords/erk1-2-phosphorylation","display_name":"ERK1/2 phosphorylation","score":0.9639999866485596},{"id":"https://openalex.org/keywords/insertional-mutagenesis","display_name":"insertional mutagenesis","score":0.8199999928474426},{"id":"https://openalex.org/keywords/cancer-cell-lines","display_name":"cancer cell lines","score":0.6029999852180481},{"id":"https://openalex.org/keywords/anticancer-drug-mechanism","display_name":"anticancer drug mechanism","score":0.460999995470047}],"concepts":[{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.7842303514480591},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.6534640789031982},{"id":"https://openalex.org/C2777553839","wikidata":"https://www.wikidata.org/wiki/Q14330986","display_name":"Tyrosine phosphorylation","level":3,"score":0.5817205905914307},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.5685201287269592},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.5290462374687195},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.521782398223877},{"id":"https://openalex.org/C2777730290","wikidata":"https://www.wikidata.org/wiki/Q411114","display_name":"NF-\u03baB","level":3,"score":0.5146711468696594},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5022516250610352},{"id":"https://openalex.org/C2779730028","wikidata":"https://www.wikidata.org/wiki/Q15325101","display_name":"I\u03baB\u03b1","level":4,"score":0.47577396035194397},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.4289546310901642},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.4206453859806061},{"id":"https://openalex.org/C2776165026","wikidata":"https://www.wikidata.org/wiki/Q188017","display_name":"Tyrosine","level":2,"score":0.41501113772392273},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3921129107475281},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3493785858154297},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3322029113769531},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.15721583366394043},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D002470","descriptor_name":"Cell Survival","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D004815","descriptor_name":"Epidermal Growth Factor","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011796","descriptor_name":"Quinacrine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015854","descriptor_name":"Up-Regulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015870","descriptor_name":"Gene Expression","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051057","descriptor_name":"Proto-Oncogene Proteins c-akt","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D066246","descriptor_name":"ErbB Receptors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1073/pnas.1105369108","doi":"https://doi.org/10.1073/pnas.1105369108","is_oa":false,"landing_page_url":"https://doi.org/10.1073/pnas.1105369108","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:3093511","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3093511","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proc Natl Acad Sci U S A","raw_type":"Text"},{"id":"pmid:21518868","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/21518868","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Journal Article"}],"best_oa_location":{"id":"pmh:oai:pubmedcentral.nih.gov:3093511","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3093511","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proc Natl Acad Sci U S A","raw_type":"Text"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.8199999928474426,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G5499462947","display_name":"Activators and repressors of NFkappaB and IRF3/7 in innate immunity","funder_award_id":"R01CA095851","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":42,"referenced_works":["https://openalex.org/W1514134885","https://openalex.org/W1617532721","https://openalex.org/W1931416869","https://openalex.org/W1971889132","https://openalex.org/W1978154545","https://openalex.org/W1984795762","https://openalex.org/W1985101923","https://openalex.org/W1988924112","https://openalex.org/W1994170326","https://openalex.org/W1994275338","https://openalex.org/W2001306989","https://openalex.org/W2002191849","https://openalex.org/W2007058107","https://openalex.org/W2007618944","https://openalex.org/W2014783058","https://openalex.org/W2015723871","https://openalex.org/W2016108022","https://openalex.org/W2019822560","https://openalex.org/W2020359797","https://openalex.org/W2026863172","https://openalex.org/W2031019010","https://openalex.org/W2035191293","https://openalex.org/W2035253718","https://openalex.org/W2037680322","https://openalex.org/W2044618871","https://openalex.org/W2048582801","https://openalex.org/W2049896044","https://openalex.org/W2052627441","https://openalex.org/W2055878807","https://openalex.org/W2063126618","https://openalex.org/W2065589361","https://openalex.org/W2077641794","https://openalex.org/W2089388428","https://openalex.org/W2091095196","https://openalex.org/W2092407935","https://openalex.org/W2132888121","https://openalex.org/W2145028653","https://openalex.org/W2148119611","https://openalex.org/W2156294456","https://openalex.org/W2166094088","https://openalex.org/W2166781237","https://openalex.org/W2169302611"],"related_works":["https://openalex.org/W2742840295","https://openalex.org/W2023771636","https://openalex.org/W2096564318","https://openalex.org/W2100048077","https://openalex.org/W7099606140","https://openalex.org/W2011784125","https://openalex.org/W2887298079","https://openalex.org/W1490582248","https://openalex.org/W2772593880","https://openalex.org/W2007210021"],"abstract_inverted_index":{"Quinacrine,":[0],"a":[1,47,69,167],"drug":[2,34],"with":[3,148],"antimalarial":[4],"and":[5,11,30,96,110,118,121,141,159,174],"anticancer":[6],"activities":[7],"that":[8,84,97,163,175],"inhibits":[9,131],"NF-\u03baB":[10,95,101,109,172],"activates":[12,108],"p53,":[13],"has":[14],"progressed":[15],"into":[16],"phase":[17],"II":[18],"clinical":[19],"trials":[20],"in":[21,51,145],"cancer.":[22],"To":[23],"further":[24],"elucidate":[25],"its":[26],"mechanism":[27],"of":[28,33,59,66,78,94,100,113,124,128,135,143,157],"action":[29],"identify":[31],"pathways":[32],"resistance,":[35],"we":[36],"used":[37],"an":[38,53],"unbiased":[39],"method":[40],"for":[41,180],"validation-based":[42],"insertional":[43],"mutagenesis":[44],"to":[45,74,139,154,171,183],"isolate":[46],"quinacrine-resistant":[48],"cell":[49,80],"line":[50],"which":[52],"inserted":[54],"CMV":[55],"promoter":[56],"drives":[57],"overexpression":[58,104,142],"the":[60,92,132],"FER":[61,67,103,125,137,144,164],"tyrosine":[62],"kinase":[63],"(FER).":[64],"Overexpression":[65],"from":[68],"cDNA":[70],"confers":[71],"quinacrine":[72,85],"resistance":[73,182],"several":[75],"different":[76],"types":[77],"cancer":[79,87],"lines.":[81],"We":[82,161],"show":[83],"kills":[86],"cells":[88,146],"primarily":[89],"by":[90],"inhibiting":[91],"activation":[93,99,134,173],"increased":[98,155],"through":[102],"mediates":[105],"resistance.":[106],"EGF":[107,115,149],"stimulates":[111],"phosphorylation":[112,130,156],"FER,":[114],"receptor":[116],"(EGFR),":[117],"ERK":[119,129],"p42/p44,":[120],"decreased":[122],"expression":[123],"or":[126],"inhibition":[127],"EGF-induced":[133],"NF-\u03baB.":[136],"binds":[138],"EGFR,":[140],"untreated":[147],"increases":[150],"this":[151,176],"association,":[152],"leading":[153],"EGFR":[158,170],"ERK.":[160],"conclude":[162],"is":[165,178],"on":[166],"pathway":[168],"connecting":[169],"function":[177],"responsible":[179],"FER-dependent":[181],"quinacrine.":[184]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":6},{"year":2021,"cited_by_count":3},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":4},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":5},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":2}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}