{"doi":"10.1002/ijc.29012","title":"Nuclear receptors and the <scp>Warburg</scp> effect in cancer","abstract":"<jats:p>In 1927 Otto Warburg established that tumours derive energy primarily from the conversion of glucose to lactic acid and only partially through cellular respiration involving oxygen. In the 1950s he proposed that all causes of cancer reflected different mechanisms of disabling cellular respiration in favour of fermentation (now termed aerobic glycolysis). The role of aberrant glucose metabolism in cancer is now firmly established. The shift away from oxidative phosphorylation towards the metabolically expensive aerobic glycolysis is somewhat counter‐intuitive given its wasteful nature. Multiple control processes are in place to maintain cellular efficiency and it is likely that these mechanisms are disrupted to facilitate the shift to the reliance on aerobic glycolysis. One such process of cell control is mediated by the nuclear receptor superfamily. This large family of transcription factors plays a significant role in sensing environmental cues and controlling decisions on proliferation, differentiation and cell death for example, to regulate glucose uptake and metabolism and to modulate the actions of oncogenes and tumour suppressors. In this review we highlight mechanisms by which nuclear receptors actions are altered during tumorigenic transformation and can serve to enhance the shift to aerobic glycolysis. At the simplest level, a basic alteration in NR behaviour can serve to enhance glycolytic flux thus providing a basis for enhanced survival within the tumour micro‐environment. Ameliorating the enhanced NR activity in this context may help to sensitize cancer cells to Warburg targeted therapies and may provide future drug targets.</jats:p>","journal":"International Journal of Cancer","year":2015,"id":635874,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"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":325040,"name":"Moray J. Campbell","orcid":"0000-0002-3355-0928","position":1,"is_corresponding":false},{"id":564954,"name":"James L. Thorne","orcid":"0000-0002-3037-8528","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nuclear receptors and the <scp>Warburg</scp> effect in cancer","abstract":"<jats:p>In 1927 Otto Warburg established that tumours derive energy primarily from the conversion of glucose to lactic acid and only partially through cellular respiration involving oxygen. In the 1950s he proposed that all causes of cancer reflected different mechanisms of disabling cellular respiration in favour of fermentation (now termed aerobic glycolysis). The role of aberrant glucose metabolism in cancer is now firmly established. The shift away from oxidative phosphorylation towards the metabolically expensive aerobic glycolysis is somewhat counter‐intuitive given its wasteful nature. Multiple control processes are in place to maintain cellular efficiency and it is likely that these mechanisms are disrupted to facilitate the shift to the reliance on aerobic glycolysis. One such process of cell control is mediated by the nuclear receptor superfamily. This large family of transcription factors plays a significant role in sensing environmental cues and controlling decisions on proliferation, differentiation and cell death for example, to regulate glucose uptake and metabolism and to modulate the actions of oncogenes and tumour suppressors. In this review we highlight mechanisms by which nuclear receptors actions are altered during tumorigenic transformation and can serve to enhance the shift to aerobic glycolysis. At the simplest level, a basic alteration in NR behaviour can serve to enhance glycolytic flux thus providing a basis for enhanced survival within the tumour micro‐environment. Ameliorating the enhanced NR activity in this context may help to sensitize cancer cells to Warburg targeted therapies and may provide future drug targets.</jats:p>","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24895240","pmcid":"PMC4790452","openalex_id":"https://openalex.org/W1929233229","authors":[],"funders":[{"funder_name":"NucSys, a European Community FP6-Marie Curie Research Training Network, the Biotechnology and Biological Sciences Research Council","grant_id":"BB/D523651/1","title":null},{"funder_name":"National Institute of Health grants","grant_id":"R01 CA095367-06 and 2R01-CA-095045-06","title":null},{"funder_name":"NCI Cancer Center Support Grant to the Roswell Park Cancer Institute","grant_id":"CA016056","title":null},{"funder_name":"NCI Cancer Center Support Grant to the Roswell Park Cancer Institute","grant_id":"LPP064","title":null},{"funder_name":"NCI NIH HHS","grant_id":"2R01-CA-095045-06","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01CA095367-06","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA016056","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA095045","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA095367","title":null},{"funder_name":"Breast Cancer Research Action Group","grant_id":"","title":null}],"total_grants":10,"fwci":1.5933,"citation_percentile":0.81152052,"influential_citations":0,"citation_trend":[{"year":2014,"count":3},{"year":2015,"count":4},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2019,"count":2},{"year":2020,"count":3},{"year":2021,"count":7},{"year":2022,"count":6},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.29012","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.29012","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fijc.29012","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.29012","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ijc.29012","host_type":"publisher"},{"url":"https://doi.org/10.1002/ijc.29012","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24895240","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4790452","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4790452","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4790452?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer, Hypoxia, and Metabolism","ATP Synthase and ATPases Research","Neuroblastoma Research and Treatments"],"mesh_terms":["Animals","Energy Metabolism","Humans","Neoplasms","Receptors, Cytoplasmic and Nuclear"],"keywords":["Warburg effect","Anaerobic glycolysis","Glycolysis","Cancer cell","Biology","Cellular respiration","Context (archaeology)","Cell biology","Oxidative phosphorylation","Neoplastic transformation","Cancer","Biochemistry","Mitochondrion","Metabolism","Carcinogenesis","Genetics","Nuclear Receptors","Energy Regulation"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.15020768.v1","title":"Additional file 1 of Pseudoginsengenin DQ exerts antitumour activity against hypopharyngeal cancer cells by targeting the HIF-1α-GLUT1 pathway","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.15020768","title":"Additional file 1 of Pseudoginsengenin DQ exerts antitumour activity against hypopharyngeal cancer cells by targeting the HIF-1α-GLUT1 pathway","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:44:02.020254Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}