{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:24:48Z","timestamp":1792095888643,"version":"4.4.0"},"reference-count":130,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2022-NR070154"],"award-info":[{"award-number":["RS-2022-NR070154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Endometriosis is a chronic gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, leading to inflammation, pain, and infertility. Emerging evidence indicates that endometriotic lesions exhibit cancer-like properties, including metabolic reprogramming marked by increased glucose uptake, enhanced Warburg\u2019s effect, and altered mitochondrial function. These metabolic adaptations support cell survival under hypoxic conditions and contribute to immune evasion and sustained proliferation. This review summarizes current findings on the molecular mechanisms driving metabolic reprogramming in endometriosis, including the roles of mitochondrial dysfunction, hypoxia-inducible factor (HIF) signaling, the PI3K\/AKT\/mTOR pathway, inflammatory cytokines, and genetic and epigenetic regulators. In addition, we discuss therapeutic strategies targeting glycolytic pathways using both synthetic inhibitors and natural compounds, which represent promising non-hormonal options. Finally, we highlight the need for further preclinical and clinical studies to validate metabolic interventions and improve outcomes for patients with endometriosis.<\/jats:p>","DOI":"10.3390\/ph18060813","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T04:46:38Z","timestamp":1748493998000},"page":"813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Warburg-like Metabolic Reprogramming in Endometriosis: From Molecular Mechanisms to Therapeutic Approaches"],"prefix":"10.3390","volume":"18","author":[{"given":"Bo-Sung","family":"Kim","sequence":"first","affiliation":[{"name":"Research Institute for Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-3119","authenticated-orcid":false,"given":"Bosung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyeong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0442-4604","authenticated-orcid":false,"given":"Wonyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Research Institute for Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8975-0876","authenticated-orcid":false,"given":"Sung-Jin","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-1512","authenticated-orcid":false,"given":"Jongkil","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Pusan National University Hospital, Busan 49241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonnam","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-0171","authenticated-orcid":false,"given":"Ki-Tae","family":"Ha","sequence":"additional","affiliation":[{"name":"Research Institute for Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"},{"name":"Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","article-title":"Clinical practice. Endometriosis","volume":"362","author":"Giudice","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/humrep\/des073","article-title":"The burden of endometriosis: Costs and quality of life of women with endometriosis and treated in referral centres","volume":"27","author":"Simoens","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_3","unstructured":"World Health Organization (WHO) (2025, May 26). Endometriosis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/endometriosis."},{"key":"ref_4","first-page":"349","article-title":"Endometriosis still a challenge","volume":"7","author":"Mehedintu","year":"2014","journal-title":"J. Med. Life"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00404-015-3875-y","article-title":"Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data","volume":"293","author":"Ping","year":"2016","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1080\/14656566.2018.1494154","article-title":"Current and emerging treatment options for endometriosis","volume":"19","author":"Ferrero","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/humupd\/dmp007","article-title":"Recurrence of endometriosis and its control","volume":"15","author":"Guo","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"158490","DOI":"10.1155\/2015\/158490","article-title":"The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects","volume":"2015","author":"Hughes","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000052872","article-title":"Evidence that endometriosis behaves in a malignant manner","volume":"50","author":"Thomas","year":"2000","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1210\/jc.2014-1026","article-title":"Transforming growth factor-beta induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis","volume":"99","author":"Young","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1093\/biolre\/ioac081","article-title":"Downregulating HK2 inhibits proliferation of endometrial stromal cells through a noncanonical pathway involving phosphorylation of signal transducer and activator of transcription 1 in endometriosis","volume":"107","author":"Hou","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: How does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcancer.2008.11.006","article-title":"Hexokinase-2 bound to mitochondria: Cancer\u2019s stygian link to the \u201cWarburg Effect\u201d and a pivotal target for effective therapy","volume":"19","author":"Mathupala","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3389\/fonc.2020.00159","article-title":"Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis","volume":"10","author":"Zahra","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s11033-015-3858-x","article-title":"Cancer metabolism and the Warburg effect: The role of HIF-1 and PI3K","volume":"42","author":"Courtnay","year":"2015","journal-title":"Mol. Biol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-020-00235-2","article-title":"Regulation of cancer cell metabolism: Oncogenic MYC in the driver\u2019s seat","volume":"5","author":"Dong","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1038\/ncomms3935","article-title":"Tumour-associated mutant p53 drives the Warburg effect","volume":"4","author":"Zhang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2045-3701-3-9","article-title":"The regulation of cellular metabolism by tumor suppressor p53","volume":"3","author":"Liang","year":"2013","journal-title":"Cell Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2049-3002-2-1","article-title":"TIGAR, TIGAR, burning bright","volume":"2","author":"Lee","year":"2014","journal-title":"Cancer Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/aps.2010.151","article-title":"The role of p53 in cell metabolism","volume":"31","author":"Zhang","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.molcel.2016.02.011","article-title":"Mitochondria and Cancer","volume":"61","author":"Zong","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1158\/2159-8290.CD-20-0844","article-title":"Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy","volume":"10","author":"Fendt","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trecan.2017.01.005","article-title":"Glutamine Metabolism in Cancer: Understanding the Heterogeneity","volume":"3","author":"Cluntun","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ccell.2023.01.009","article-title":"Metabolic programming and immune suppression in the tumor microenvironment","volume":"41","author":"Arner","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ohshima, K., and Morii, E. (2021). Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis. Metabolites, 11.","DOI":"10.3390\/metabo11010028"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Schiliro, C., and Firestein, B.L. (2021). Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation. Cells, 10.","DOI":"10.3390\/cells10051056"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1038\/s42003-024-06713-5","article-title":"Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level","volume":"7","author":"Sarsenova","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s10815-023-02769-0","article-title":"Establishment of a novel glycolysis-immune-related diagnosis gene signature for endometriosis by machine learning","volume":"40","author":"Chen","year":"2023","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3357","DOI":"10.1007\/s43032-024-01518-7","article-title":"Correlation of Glycolysis-immune-related Genes in the Follicular Microenvironment of Endometriosis Patients with ART Outcomes","volume":"31","author":"Guo","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Toniyan, K.A., Malkov, A.A., Biryukov, N.S., Gorbacheva, E.Y., Boyarintsev, V.V., and Ogneva, I.V. (2024). The Cellular Respiration of Endometrial Biopsies from Patients with Various Forms of Endometriosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073680"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Khashchenko, E.P., Vysokikh, M.Y., Marey, M.V., Sidorova, K.O., Manukhova, L.A., Shkavro, N.N., Uvarova, E.V., Chuprynin, V.D., Fatkhudinov, T.K., and Adamyan, L.V. (2024). Altered Glycolysis, Mitochondrial Biogenesis, Autophagy and Apoptosis in Peritoneal Endometriosis in Adolescents. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084238"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1529074","DOI":"10.3389\/fmed.2025.1529074","article-title":"Identification of fatty acid metabolism hub genes in endometriosis using integrative bioinformatics analysis","volume":"12","author":"Tu","year":"2025","journal-title":"Front. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s10020-024-00834-7","article-title":"IGF2BP3 promotes glutamine metabolism of endometriosis by interacting with UCA1 to enhances the mRNA stability of GLS1","volume":"30","author":"Wang","year":"2024","journal-title":"Mol. Med."},{"key":"ref_37","first-page":"309","article-title":"Pathological functions of hypoxia in endometriosis","volume":"7","author":"Hsiao","year":"2015","journal-title":"Front. Biosci. (Elite Ed.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"F19","DOI":"10.1530\/REP-20-0267","article-title":"HYPOXIA AND REPRODUCTIVE HEALTH: The role of hypoxia in the development and progression of endometriosis","volume":"161","author":"Li","year":"2021","journal-title":"Reproduction"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1530\/REP-19-0615","article-title":"Transcriptomic responses to hypoxia in endometrial and decidual stromal cells","volume":"160","author":"Rytkonen","year":"2020","journal-title":"Reproduction"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/path.5314","article-title":"Oncogenic mutations in histologically normal endometrium: The new normal?","volume":"249","author":"Lac","year":"2019","journal-title":"J. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.celrep.2018.07.037","article-title":"Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium","volume":"24","author":"Suda","year":"2018","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.rbmo.2020.09.002","article-title":"The follicular fluid metabolome differs according to the endometriosis phenotype","volume":"41","author":"Santulli","year":"2020","journal-title":"Reprod. Biomed. Online"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1530\/JME-13-0194","article-title":"Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions","volume":"52","author":"McKinnon","year":"2014","journal-title":"J. Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/JP280572","article-title":"Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology","volume":"599","author":"Kierans","year":"2021","journal-title":"J. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4048\/jbc.2018.21.e42","article-title":"Hypoxia-Inducible Factor 1alpha Regulates the Transforming Growth Factor beta1\/SMAD Family Member 3 Pathway to Promote Breast Cancer Progression","volume":"21","author":"Peng","year":"2018","journal-title":"J. Breast Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.31083\/j.fbl2912417","article-title":"The PKM2\/HIF-1alpha Axis is Involved in the Pathogenesis of Endometriosis via TGF-beta1 under Endometrial Polyps","volume":"29","author":"Li","year":"2024","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1465393","DOI":"10.3389\/fendo.2024.1465393","article-title":"Hypoxic conditions affect transcriptome of endometrial stromal cells in endometriosis and promote TGFBI axis","volume":"15","author":"Sarsenova","year":"2024","journal-title":"Front. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1172\/JCI57322","article-title":"Endothelial HIF-2alpha regulates murine pathological angiogenesis and revascularization processes","volume":"122","author":"Skuli","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1038\/onc.2008.160","article-title":"Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice","volume":"27","author":"Rankin","year":"2008","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fonc.2017.00286","article-title":"Non-Canonical Mechanisms Regulating Hypoxia-Inducible Factor 1 Alpha in Cancer","volume":"7","author":"Iommarini","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2353\/ajpath.2009.080804","article-title":"Reactive oxygen species controls endometriosis progression","volume":"175","author":"Ngo","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103205","DOI":"10.1016\/j.redox.2024.103205","article-title":"Hypoxia and the endometrium: An indispensable role for HIF-1\u03b1 as therapeutic strategies","volume":"73","author":"Dai","year":"2024","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1096\/fj.03-0329fje","article-title":"IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB\/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis","volume":"17","author":"Jung","year":"2003","journal-title":"FASEB J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"806650","DOI":"10.3389\/fmolb.2021.806650","article-title":"Accumulated ROS Activates HIF-1alpha-Induced Glycolysis and Exerts a Protective Effect on Sensory Hair Cells Against Noise-Induced Damage","volume":"8","author":"Liang","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-kappaB in Oxidative Stress","volume":"7","author":"Lingappan","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7702681","DOI":"10.1155\/2022\/7702681","article-title":"The Role of PKM2 in the Regulation of Mitochondrial Function: Focus on Mitochondrial Metabolism, Oxidative Stress, Dynamic, and Apoptosis. PKM2 in Mitochondrial Function","volume":"2022","author":"Gao","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.1111\/bph.14391","article-title":"Inhibition of PI3K\/AKT\/mTOR pathway for the treatment of endometriosis","volume":"175","author":"Barra","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/09513590.2011.583955","article-title":"PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: An update","volume":"28","author":"Makker","year":"2012","journal-title":"Gynecol. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"120805","DOI":"10.1016\/j.lfs.2022.120805","article-title":"Role of AMPK\/mTOR, mitochondria, and ROS in the pathogenesis of endometriosis","volume":"306","author":"Assaf","year":"2022","journal-title":"Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/pros.23972","article-title":"Proteomic and transcriptomic profiling of Pten gene-knockout mouse model of prostate cancer","volume":"80","author":"Zhang","year":"2020","journal-title":"Prostate"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10585-019-09998-7","article-title":"PTEN loss activates a functional AKT\/CXCR4 signaling axis to potentiate tumor growth and lung metastasis in human osteosarcoma cells","volume":"37","author":"Xi","year":"2020","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/biolre\/ioaf016","article-title":"Phosphatase and tensin homolog deficiency induces M2 macrophage polarization by promoting glycolytic activity in endometrial stromal cells","volume":"112","author":"Dai","year":"2025","journal-title":"Biol. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13045-018-0674-5","article-title":"The PIK3CA E542K and E545K mutations promote glycolysis and proliferation via induction of the beta-catenin\/SIRT3 signaling pathway in cervical cancer","volume":"11","author":"Jiang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/molehr\/gaw045","article-title":"ID2 mediates the transforming growth factor-beta1-induced Warburg-like effect seen in the peritoneum of women with endometriosis","volume":"22","author":"Young","year":"2016","journal-title":"Mol. Hum. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1210\/en.2014-1591","article-title":"TNF-\u03b1-induced NF-\u03baB activation stimulates skeletal muscle glycolytic metabolism through activation of HIF-1\u03b1","volume":"156","author":"Remels","year":"2015","journal-title":"Endocrinology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.3390\/cancers6031579","article-title":"STAT3 Activities and Energy Metabolism: Dangerous Liaisons","volume":"6","author":"Camporeale","year":"2014","journal-title":"Cancers"},{"key":"ref_67","first-page":"1287","article-title":"Inflammatory cytokine profile of co-cultivated primary cells from the endometrium of women with and without endometriosis","volume":"18","author":"Schor","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_68","first-page":"105","article-title":"Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro","volume":"37","author":"Taylor","year":"1992","journal-title":"Circ. Shock"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3389\/fimmu.2018.01742","article-title":"Human Plasmablast Migration Toward CXCL12 Requires Glucose Oxidation by Enhanced Pyruvate Dehydrogenase Activity via AKT","volume":"9","author":"Pak","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Luker, K.E., and Luker, G.D. (2022). The CXCL12\/CXCR4\/ACKR3 Signaling Axis Regulates PKM2 and Glycolysis. Cells, 11.","DOI":"10.3390\/cells11111775"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15149","DOI":"10.1038\/s41598-021-94474-0","article-title":"Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock","volume":"11","author":"Valente","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s10753-020-01240-x","article-title":"Phosphoproteomics and Proteomics Reveal Metabolism as a Key Node in LPS-Induced Acute Inflammation in RAW264.7","volume":"43","author":"Luo","year":"2020","journal-title":"Inflammation"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1161\/ATVBAHA.120.314037","article-title":"Metabolic Reprogramming in Immune Response and Tissue Inflammation","volume":"40","author":"Sun","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Penariol, L.B., Thom\u00e9, C.H., Tozetti, P.A., Paier, C.R., Buono, F.O., Peronni, K.C., Orellana, M.D., Covas, D.T., Moraes, M.E., and Silva, W.A. (2022). What do the transcriptome and proteome of menstrual blood-derived mesenchymal stem cells tell us about endometriosis?. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202209.0180.v1"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1021\/acs.jproteome.5b00965","article-title":"Deep Quantitative Proteomics Reveals Extensive Metabolic Reprogramming and Cancer-Like Changes of Ectopic Endometriotic Stromal Cells","volume":"15","author":"Kasvandik","year":"2016","journal-title":"J. Proteome Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15539","DOI":"10.1038\/ncomms15539","article-title":"Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism","volume":"8","author":"Sapkota","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13148-025-01828-w","article-title":"Systematic review on the DNA methylation role in endometriosis: Current evidence and perspectives","volume":"17","author":"Ducreux","year":"2025","journal-title":"Clin. Epigenet."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zubrzycka, A., Zubrzycki, M., Perdas, E., and Zubrzycka, M. (2020). Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051309"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.fertnstert.2012.11.055","article-title":"MicroRNA miR-145 inhibits proliferation, invasiveness, and stem cell phenotype of an in vitro endometriosis model by targeting multiple cytoskeletal elements and pluripotency factors","volume":"99","author":"Adammek","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_80","first-page":"1135","article-title":"MicroRNAs in endometriosis: Biological function and emerging biomarker candidatesdagger","volume":"100","author":"Bjorkman","year":"2019","journal-title":"Biol. Reprod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/humrep\/deu332","article-title":"Enhanced miR-210 expression promotes the pathogenesis of endometriosis through activation of signal transducer and activator of transcription 3","volume":"30","author":"Okamoto","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.2147\/CMAR.S314502","article-title":"Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives","volume":"13","author":"Huang","year":"2021","journal-title":"Cancer Manag. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1158\/0008-5472.CAN-18-1432","article-title":"Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2","volume":"79","author":"Malakar","year":"2019","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.2147\/OTT.S316597","article-title":"Circular RNAs Regulate Glucose Metabolism in Cancer Cells","volume":"14","author":"Ji","year":"2021","journal-title":"Onco Targets Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"998417","DOI":"10.3389\/fgene.2022.998417","article-title":"Identification of functional TF-miRNA-hub gene regulatory network associated with ovarian endometriosis","volume":"13","author":"Li","year":"2022","journal-title":"Front. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e240018","DOI":"10.1530\/REP-24-0018","article-title":"Highly expressed lncRNA H19 in endometriosis promotes aerobic glycolysis and histone lactylation","volume":"168","author":"Wen","year":"2024","journal-title":"Reproduction"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.rbmo.2014.09.004","article-title":"Knockdown of prohibitin expression promotes glucose metabolism in eutopic endometrial stromal cells from women with endometriosis","volume":"29","author":"Qi","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"gaac018","DOI":"10.1093\/molehr\/gaac018","article-title":"Elevated prohibitin 1 expression mitigates glucose metabolism defects in granulosa cells of infertile patients with endometriosis","volume":"28","author":"Mao","year":"2022","journal-title":"Mol. Hum. Reprod."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Signorile, A., Sgaramella, G., Bellomo, F., and De Rasmo, D. (2019). Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases. Cells, 8.","DOI":"10.3390\/cells8010071"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-024-01839-8","article-title":"Mitochondrial dysfunction: Mechanisms and advances in therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e30952","DOI":"10.7554\/eLife.30952","article-title":"Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals","volume":"6","author":"Kuhl","year":"2017","journal-title":"eLife"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1111\/jog.15791","article-title":"The role of mitochondrial dynamics in the pathophysiology of endometriosis","volume":"49","author":"Kobayashi","year":"2023","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.biochi.2016.01.006","article-title":"Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis","volume":"123","author":"Zhan","year":"2016","journal-title":"Biochimie"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6921","DOI":"10.1158\/0008-5472.CAN-11-1457","article-title":"Lactate: A metabolic key player in cancer","volume":"71","author":"Hirschhaeuser","year":"2011","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1039\/C7MB00181A","article-title":"Metabolomic profiling and biochemical evaluation of the follicular fluid of endometriosis patients","volume":"13","author":"Marianna","year":"2017","journal-title":"Mol. Biosyst."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ke, J., Ye, J., Li, M., and Zhu, Z. (2021). The Role of Matrix Metalloproteinases in Endometriosis: A Potential Target. Biomolecules, 11.","DOI":"10.3390\/biom11111739"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Niland, S., Riscanevo, A.X., and Eble, J.A. (2021). Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010146"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/1933719118789513","article-title":"Induction of Pyruvate Dehydrogenase Kinase 1 by Hypoxia Alters Cellular Metabolism and Inhibits Apoptosis in Endometriotic Stromal Cells","volume":"26","author":"Lee","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"25389","DOI":"10.1073\/pnas.1916144116","article-title":"Repurposing dichloroacetate for the treatment of women with endometriosis","volume":"116","author":"Horne","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s40814-021-00797-0","article-title":"Dichloroacetate as a possible treatment for endometriosis-associated pain: A single-arm open-label exploratory clinical trial (EPiC)","volume":"7","author":"Leow","year":"2021","journal-title":"Pilot Feasibility Stud."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3892\/etm.2021.9788","article-title":"Caesalpinia sappan induces apoptotic cell death in ectopic endometrial 12Z cells through suppressing pyruvate dehydrogenase kinase 1 expression","volume":"21","author":"Kim","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"110406","DOI":"10.1016\/j.cellsig.2022.110406","article-title":"FTO-dependent N(6)-Methyladenosine regulates the progression of endometriosis via the ATG5\/PKM2 Axis","volume":"98","author":"Wang","year":"2022","journal-title":"Cell Signal."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3892\/mmr.2021.12276","article-title":"Hypoxia-induced lactate dehydrogenase A protects cells from apoptosis in endometriosis","volume":"24","author":"Zheng","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"872810","DOI":"10.3389\/fphar.2022.872810","article-title":"Water-Extracted Prunella vulgaris Alleviates Endometriosis by Reducing Aerobic Glycolysis","volume":"13","author":"Cho","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1275000","DOI":"10.3389\/fphar.2023.1275000","article-title":"Natural compounds as lactate dehydrogenase inhibitors: Potential therapeutics for lactate dehydrogenase inhibitors-related diseases","volume":"14","author":"Han","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"BSR20211828","DOI":"10.1042\/BSR20211828","article-title":"Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-kappaB-induced transcription of PKM2","volume":"9","author":"Yao","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1007\/s43032-023-01208-w","article-title":"PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis","volume":"30","author":"Wang","year":"2023","journal-title":"Reprod. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/s41419-022-05241-6","article-title":"Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis","volume":"13","author":"Lu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1007\/s11684-024-1069-3","article-title":"PAK5-mediated PKM2 phosphorylation is critical for anaerobic glycolysis in endometriosis","volume":"18","author":"Lu","year":"2024","journal-title":"Front. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9864963","DOI":"10.1155\/2018\/9864963","article-title":"Understanding the Role of Gui-Zhi-Fu-Ling-Capsules (Chinese Medicine) for Treatment of Endometriosis in the Rat Model: Using NMR Based Metabolomics","volume":"2018","author":"Zhou","year":"2018","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"119230","DOI":"10.1016\/j.lfs.2021.119230","article-title":"Effects of atorvastatin and resveratrol against the experimental endometriosis; evidence for glucose and monocarboxylate transporters, neoangiogenesis","volume":"272","author":"Bahrami","year":"2021","journal-title":"Life Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12958-021-00770-9","article-title":"HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression","volume":"19","author":"Wang","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"105363","DOI":"10.1016\/j.isci.2022.105363","article-title":"Ovarian tumorB1-mediated heat shock transcription factor 1 deubiquitination is critical for glycolysis and development of endometriosis","volume":"25","author":"Ling","year":"2022","journal-title":"iScience"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00018-022-04637-z","article-title":"CHIP induces ubiquitination and degradation of HMGB1 to regulate glycolysis in ovarian endometriosis","volume":"80","author":"Sun","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/imm.13574","article-title":"Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3\/Trib1\/ERK\/STAT3 signalling pathway in endometriosis","volume":"168","author":"Gou","year":"2023","journal-title":"Immunology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"112083","DOI":"10.1016\/j.mce.2023.112083","article-title":"PFKFB3 promotes endometriosis cell proliferation via enhancing the protein stability of beta-catenin","volume":"579","author":"Ling","year":"2024","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"bqae018","DOI":"10.1210\/endocr\/bqae018","article-title":"AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERbeta","volume":"165","author":"Sun","year":"2024","journal-title":"Endocrinology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/imm.13786","article-title":"The dysfunction of CD8(+) T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis","volume":"172","author":"Huang","year":"2024","journal-title":"Immunology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"104312","DOI":"10.1016\/j.jri.2024.104312","article-title":"Integrin beta3 enhances glycolysis and increases lactate production in endometriosis","volume":"165","author":"Gao","year":"2024","journal-title":"J. Reprod. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-020-00251-y","article-title":"Metabolic reprogramming in macrophage responses","volume":"9","author":"Liu","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"118190","DOI":"10.1016\/j.jep.2024.118190","article-title":"Potential Mechanisms of Guizhi Fuling Wan in Treating Endometriosis: An Analysis Based on TCMSP and DisGeNET Databases","volume":"329","author":"Yee","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1080\/00016340903176826","article-title":"Endometriosis-associated nerve fibers and pain","volume":"88","author":"Medina","year":"2009","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_124","first-page":"e11516","article-title":"Inflammation to Infertility: Panoramic View on Endometriosis","volume":"12","author":"Hamid","year":"2020","journal-title":"Cureus"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1226687","DOI":"10.3389\/fendo.2023.1226687","article-title":"Decreased oocyte quality in patients with endometriosis is closely related to abnormal granulosa cells","volume":"14","author":"Fan","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejogrb.2020.12.044","article-title":"Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics","volume":"258","author":"Kobayashi","year":"2021","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"7265238","DOI":"10.1155\/2017\/7265238","article-title":"Oxidative Stress and Endometriosis: A Systematic Review of the Literature","volume":"2017","author":"Scutiero","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Song, S.Y., Jung, Y.W., Shin, W., Park, M., Lee, G.W., Jeong, S., An, S., Kim, K., Ko, Y.B., and Lee, K.H. (2023). Endometriosis-Related Chronic Pelvic Pain. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102868"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1186\/s12905-021-01545-5","article-title":"Treatment of endometriosis: A review with comparison of 8 guidelines","volume":"21","author":"Kalaitzopoulos","year":"2021","journal-title":"BMC Womens Health"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"102311","DOI":"10.1016\/j.coph.2022.102311","article-title":"Hormonal drugs for the treatment of endometriosis","volume":"67","author":"Capezzuoli","year":"2022","journal-title":"Curr. Opin. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/6\/813\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:17Z","timestamp":1760031737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/6\/813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":130,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ph18060813"],"URL":"https:\/\/doi.org\/10.3390\/ph18060813","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}