{"id":"https://openalex.org/W4282958505","doi":"https://doi.org/10.1158/1538-7445.am2022-2376","title":"Abstract 2376: Pyruvate carboxylase regulates mammary tumor microenvironment composition via central carbon metabolism","display_name":"Abstract 2376: Pyruvate carboxylase regulates mammary tumor microenvironment composition via central carbon metabolism","publication_year":2022,"publication_date":"2022-06-15","ids":{"openalex":"https://openalex.org/W4282958505","doi":"https://doi.org/10.1158/1538-7445.am2022-2376"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2022-2376","doi":"https://doi.org/10.1158/1538-7445.am2022-2376","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-2376","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5083930279","display_name":"Alexander J. Pfeil","orcid":"https://orcid.org/0000-0002-5159-019X","observed_orcids":["https://orcid.org/0000-0002-5159-019X"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alexander J. Pfeil","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058311217","display_name":"Michael F. Coleman","orcid":"https://orcid.org/0000-0002-6914-848X","observed_orcids":["https://orcid.org/0000-0002-6914-848X"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael F. Coleman","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029058014","display_name":"Eylem Kulkoyluoglu\u2010Cotul","orcid":"https://orcid.org/0000-0003-2398-2441","observed_orcids":["https://orcid.org/0000-0003-2398-2441"]},"institutions":[{"id":"https://openalex.org/I219193219","display_name":"Purdue University West Lafayette","ror":"https://ror.org/02dqehb95","country_code":"US","type":"education","lineage":["https://openalex.org/I219193219"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eylem Kulkoyluoglu-Cotul","raw_affiliation_strings":["2Purdue University, West Lafayette, IN"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Purdue University, West Lafayette, IN","institution_ids":["https://openalex.org/I219193219"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003724678","display_name":"Violet A. Kiesel","orcid":"https://orcid.org/0000-0003-4059-9110","observed_orcids":["https://orcid.org/0000-0003-4059-9110"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Violet Kiesel","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023310320","display_name":"Emily N. Devericks","orcid":"https://orcid.org/0000-0003-0986-7842","observed_orcids":["https://orcid.org/0000-0003-0986-7842"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Emily Devericks","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003287764","display_name":"Suhas K. Etigunta","orcid":"https://orcid.org/0000-0003-2946-0767","observed_orcids":["https://orcid.org/0000-0003-2946-0767"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Suhas K. Etigunta","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026812062","display_name":"Dorothy Teegarden","orcid":"https://orcid.org/0000-0002-7045-3748","observed_orcids":["https://orcid.org/0000-0002-7045-3748"]},"institutions":[{"id":"https://openalex.org/I219193219","display_name":"Purdue University West Lafayette","ror":"https://ror.org/02dqehb95","country_code":"US","type":"education","lineage":["https://openalex.org/I219193219"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dorothy Teegarden","raw_affiliation_strings":["2Purdue University, West Lafayette, IN"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Purdue University, West Lafayette, IN","institution_ids":["https://openalex.org/I219193219"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090843213","display_name":"Michael K. Wendt","orcid":"https://orcid.org/0000-0002-3665-7413","observed_orcids":["https://orcid.org/0000-0002-3665-7413"]},"institutions":[{"id":"https://openalex.org/I219193219","display_name":"Purdue University West Lafayette","ror":"https://ror.org/02dqehb95","country_code":"US","type":"education","lineage":["https://openalex.org/I219193219"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael K. Wendt","raw_affiliation_strings":["2Purdue University, West Lafayette, IN"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Purdue University, West Lafayette, IN","institution_ids":["https://openalex.org/I219193219"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5036400845","display_name":"Stephen David Hursting","orcid":"https://orcid.org/0000-0003-3605-2833","observed_orcids":["https://orcid.org/0000-0003-3605-2833"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Stephen D. Hursting","raw_affiliation_strings":["1The University of North Carolina at Chapel Hill, Chapel Hill, NC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1The University of North Carolina at Chapel Hill, Chapel Hill, NC;","institution_ids":["https://openalex.org/I114027177"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"82","issue":"12_Supplement","first_page":"2376","last_page":"2376"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.9955999851226807,"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/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.9955999851226807,"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/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.001500000013038516,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/T12465","display_name":"Cancer, Lipids, and Metabolism","score":0.0005000000237487257,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/pyruvate-carboxylase","display_name":"pyruvate carboxylase","score":0.9990000128746033},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.9810000061988831},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.8050000071525574},{"id":"https://openalex.org/keywords/central-carbon-metabolism","display_name":"central carbon metabolism","score":0.9200000166893005},{"id":"https://openalex.org/keywords/mitochondrial-dysfunction","display_name":"mitochondrial dysfunction","score":0.7329999804496765},{"id":"https://openalex.org/keywords/electron-transport-chain","display_name":"electron transport chain","score":0.7360000014305115},{"id":"https://openalex.org/keywords/lactate-metabolism","display_name":"lactate metabolism","score":0.7310000061988831},{"id":"https://openalex.org/keywords/immunosuppression","display_name":"immunosuppression","score":0.7360000014305115},{"id":"https://openalex.org/keywords/metabolic-reprogramming","display_name":"metabolic reprogramming","score":0.7990000247955322},{"id":"https://openalex.org/keywords/anaplerosis","display_name":"anaplerosis","score":0.6710000038146973},{"id":"https://openalex.org/keywords/oxidative-phosphorylation","display_name":"oxidative phosphorylation","score":0.6549999713897705},{"id":"https://openalex.org/keywords/tumor-growth","display_name":"tumor growth","score":0.4959999918937683},{"id":"https://openalex.org/keywords/shrna-knockdown","display_name":"shRNA knockdown","score":0.6790000200271606},{"id":"https://openalex.org/keywords/mass-cytometry","display_name":"mass cytometry","score":0.6690000295639038},{"id":"https://openalex.org/keywords/high-resolution-respirometry","display_name":"high-resolution respirometry","score":0.9049999713897705},{"id":"https://openalex.org/keywords/cytokine-signaling","display_name":"cytokine signaling","score":0.5419999957084656}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5812323093414307},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5656343102455139},{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.5340717434883118},{"id":"https://openalex.org/C109156525","wikidata":"https://www.wikidata.org/wiki/Q56770304","display_name":"Warburg effect","level":4,"score":0.44789135456085205},{"id":"https://openalex.org/C140137476","wikidata":"https://www.wikidata.org/wiki/Q21114968","display_name":"Pyruvate carboxylase","level":3,"score":0.4356370270252228},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.3387283682823181},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2523329257965088},{"id":"https://openalex.org/C20251656","wikidata":"https://www.wikidata.org/wiki/Q162643","display_name":"Glycolysis","level":3,"score":0.19914063811302185},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.122915118932724},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.11113446950912476}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2022-2376","doi":"https://doi.org/10.1158/1538-7445.am2022-2376","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-2376","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-3","ki-jl-3","medline","norway-2"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9476000070571899}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W3103789129","https://openalex.org/W3046934051","https://openalex.org/W4386799875","https://openalex.org/W4213065871","https://openalex.org/W2902741527","https://openalex.org/W2156337600","https://openalex.org/W4361818220","https://openalex.org/W1834469166","https://openalex.org/W3204273758","https://openalex.org/W1564105650"],"abstract_inverted_index":{"Abstract":[0],"Introduction:":[1],"Metastatic":[2],"triple-negative":[3],"breast":[4],"cancer":[5],"(TNBC)":[6],"is":[7,47,57,71],"one":[8],"of":[9,23,29,37,89,96,114,126,180,232,238,251,258,274,308,315,332,354,365,444],"the":[10,16,34,42,66,75,87,93,193,366,387,445],"deadliest":[11],"cancers":[12],"amongst":[13],"women":[14],"in":[15,74,92,105,117,153,162,219,222,285,288,317,320,324,343],"US,":[17],"with":[18,188,211,372],"a":[19,27,227,325,349],"5-year":[20],"survival":[21],"rate":[22],"12%.":[24],"Due":[25],"to":[26,49,65,79,136,279,393,399],"lack":[28],"targeted":[30],"therapies,":[31],"investigation":[32],"into":[33],"metabolic":[35,94,134,326,363],"drivers":[36],"TNBC":[38,63,97],"progression":[39],"at":[40],"both":[41],"primary":[43,76,109,290,345,367],"and":[44,100,148,177,192,207,226,245,262,272,293,304,334,348,375,396,402],"secondary":[45],"site":[46],"vital":[48,61],"direct":[50],"future":[51],"treatment":[52],"strategies.":[53],"Pyruvate":[54,430],"carboxylase":[55,431],"(PC)":[56],"an":[58,294],"anaplerotic":[59],"enzyme":[60],"for":[62,448],"metastasis":[64],"lungs,":[67],"though":[68],"its":[69,102],"expression":[70,91,104,116,229],"commonly":[72],"suppressed":[73],"tumor":[77,110,291,296,346,350,369,377,434],"compared":[78],"normal":[80],"tissue.":[81],"In":[82,132,338],"this":[83],"study,":[84],"we":[85],"investigated":[86],"role":[88],"PC":[90,115,141,217,275,283,316,340,359],"reprogramming":[95,364],"cell":[98,119,263,306],"lines":[99,120],"how":[101],"reduced":[103,223,305,335],"vivo":[106,286],"may":[107],"support":[108],"progression.":[111,378],"Methods:":[112],"Modulation":[113],"M-Wnt":[118,190,277],"was":[121,171,382],"achieved":[122],"through":[123,269],"lentiviral-mediated":[124],"transduction":[125],"PCx-targeting":[127],"short":[128],"hairpin":[129],"RNAs":[130],"(ShPC).":[131],"vitro":[133,220,318],"alterations":[135],"central":[137,438],"carbon":[138,439],"metabolism":[139,155,281,440],"following":[140,201,256],"suppression":[142,257],"were":[143,156,186,196,209,247,254],"assessed":[144,157,172],"via":[145,158,173,437],"intracellular":[146],"lactate":[147,261,270,280,333],"NAD+/NADH":[149],"assays.":[150],"Functional":[151],"shifts":[152],"mitochondrial":[154,233,252,321],"extracellular":[159],"flux":[160,268],"analysis":[161,179],"various":[163],"substrate":[164],"conditions.":[165],"Electron":[166],"transport":[167],"chain":[168],"(ETC)-intrinsic":[169],"dysfunction":[170],"high-resolution":[174],"respirometry":[175],"(HRR)":[176],"qPCR":[178],"ETC":[181,239],"gene":[182,228],"expression.":[183],"C57BL/6J":[184],"mice":[185],"injected":[187],"ShPC":[189],"cells":[191,278],"resulting":[194],"tumors":[195],"harvested":[197],"after":[198],"4":[199],"weeks":[200],"injection.":[202],"Metabolomic":[203],"analysis,":[204],"mass":[205],"cytometry,":[206],"HRR":[208],"conducted":[210],"samples":[212],"from":[213,386],"excised":[214],"tumors.":[215],"Results:":[216],"knockdown":[218,276,284,341,360],"results":[221,319],"oxygen":[224],"consumption":[225],"profile":[230],"indicative":[231,353],"dysfunction.":[234],"Genes":[235],"encoding":[236],"subunits":[237],"complexes":[240],"such":[241],"as":[242,298],"ND4FA10,":[243],"SDHB,":[244],"ATP5c1":[246],"downregulated":[248,301],"while":[249],"markers":[250],"biogenesis":[253],"upregulated":[255],"PC.":[259],"Intracellular":[260],"proliferation":[264],"assays":[265],"revealed":[266],"enhanced":[267,289,330,344,376],"dehydrogenase":[271],"sensitization":[273],"inhibitors.":[282],"resulted":[287,342],"growth":[292,347],"immunosuppressed":[295],"microenvironment,":[297],"indicated":[299],"by":[300,329,384],"cytokine":[302],"signaling":[303],"fractions":[307],"critical":[309],"anti-tumor":[310],"immune":[311,351,373],"cells.":[312],"Conclusions:":[313],"Suppression":[314],"dysfunction,":[322],"manifesting":[323],"phenotype":[327],"characterized":[328],"production":[331],"oxidative":[336],"phosphorylation.":[337],"vivo,":[339],"landscape":[352],"immunosuppression.":[355],"We":[356],"conclude":[357],"that":[358],"promotes":[361],"distinct":[362],"mammary":[368,433],"microenvironment":[370,435],"associated":[371],"evasion":[374],"Funding:":[379],"This":[380],"study":[381],"supported":[383],"grants":[385],"National":[388],"Cancer":[389,449,460],"Institute":[390],"(R35":[391],"CA197627":[392],"SD":[394,400],"Hursting,":[395],"RO1":[397],"CA232589":[398],"Hursting":[401],"D.":[403,428],"Teegarden)":[404],"Citation":[405],"Format:":[406],"Alexander":[407],"J.":[408],"Pfeil,":[409],"Michael":[410,424],"F.":[411],"Coleman,":[412],"Eylem":[413],"Kulkoyluoglu-Cotul,":[414],"Violet":[415],"Kiesel,":[416],"Emily":[417],"Devericks,":[418],"Suhas":[419],"K.":[420,425],"Etigunta,":[421],"Dorothy":[422],"Teegarden,":[423],"Wendt,":[426],"Stephen":[427],"Hursting.":[429],"regulates":[432],"composition":[436],"[abstract].":[441],"In:":[442],"Proceedings":[443],"American":[446],"Association":[447],"Research":[450],"Annual":[451],"Meeting":[452],"2022;":[453],"2022":[454],"Apr":[455],"8-13.":[456],"Philadelphia":[457],"(PA):":[458],"AACR;":[459],"Res":[461],"2022;82(12_Suppl):Abstract":[462],"nr":[463],"2376.":[464]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2025-10-10T00:00:00"}