{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:17:14Z","timestamp":1792451834781,"version":"4.5.0"},"reference-count":176,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00246603"],"award-info":[{"award-number":["RS-2023-00246603"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-25425155"],"award-info":[{"award-number":["RS-2025-25425155"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2023-00246603"],"award-info":[{"award-number":["RS-2023-00246603"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-25425155"],"award-info":[{"award-number":["RS-2025-25425155"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","award":["RS-2024-00405900"],"award-info":[{"award-number":["RS-2024-00405900"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00405900"],"award-info":[{"award-number":["RS-2024-00405900"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clear cell renal cell carcinoma (ccRCC) is increasingly recognized as a lipid-addicted malignancy in which de novo lipogenesis (DNL) supports tumor growth, survival, and treatment resistance. ccRCC-specific genetic alterations, particularly loss of VHL and activation of hypoxia-inducible factor (HIF) signaling, promote SREBP-mediated upregulation of key lipogenic enzymes, including ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA desaturase 1 (SCD1). These pathways support membrane biogenesis and redox balance while also promoting metabolic flexibility, enabling adaptation to therapeutic and microenvironmental stresses. Emerging preclinical studies suggest that pharmacological inhibition of lipogenic enzymes, either alone or in combination with tyrosine kinase inhibitors, mTOR inhibitors, HIF-2\u03b1 antagonists, or immune checkpoint blockade, may suppress ccRCC progression. However, most therapeutic data remain limited to preclinical models, and clinical validation is still lacking. This review synthesizes recent advances in molecular regulation and therapeutic targeting of DNL in ccRCC and discusses the challenges and future opportunities to improve mechanistic understanding and explore potential therapeutic applications.<\/jats:p>","DOI":"10.3390\/ijms27114924","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7430-7097","authenticated-orcid":false,"given":"Kha Cong Le","family":"Bui","sequence":"first","affiliation":[{"name":"Department of Urology B, Hue Central Hospital, Hue 49135, Vietnam"},{"name":"Division of Haematology and Oncology, Department of Internal Medicine, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"},{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4188-5778","authenticated-orcid":false,"given":"Yen Thi","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-9834","authenticated-orcid":false,"given":"Jin Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Haematology and Oncology, Department of Internal Medicine, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-7424","authenticated-orcid":false,"given":"Ji Hae","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1590\/0100-3984.2013.1927","article-title":"Renal cell carcinoma: Histological classification and correlation with imaging findings","volume":"48","author":"Muglia","year":"2015","journal-title":"Radiol. Bras."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kase, A.M., George, D.J., and Ramalingam, S. (2023). Clear cell renal cell carcinoma: From biology to treatment. Cancers, 15.","DOI":"10.3390\/cancers15030665"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/s41585-019-0211-5","article-title":"The Cancer Genome Atlas of renal cell carcinoma: Findings and clinical implications","volume":"16","author":"Linehan","year":"2019","journal-title":"Nat. Rev. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.eururo.2022.03.006","article-title":"European Association of Urology guidelines on renal cell carcinoma: The 2022 update","volume":"82","author":"Ljungberg","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_6","first-page":"1","article-title":"Surveillance strategies for renal cell carcinoma patients following nephrectomy","volume":"8","author":"Chin","year":"2006","journal-title":"Rev. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1056\/NEJMra1601333","article-title":"Systemic therapy for metastatic renal-cell carcinoma","volume":"376","author":"Choueiri","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"17","article-title":"Cancer statistics 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA A Cancer J. Clin."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","unstructured":"di Meo, N.A., Lasorsa, F., Rutigliano, M., Loizzo, D., Ferro, M., Stella, A., Bizzoca, C., Vincenti, L., Pandolfo, S.D., and Autorino, R. (2022). Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214360"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1080\/14737159.2019.1607729","article-title":"Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma","volume":"19","author":"Lucarelli","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12944-024-02024-0","article-title":"Reprogramming of lipid metabolism in the tumor microenvironment: A strategy for tumor immunotherapy","volume":"23","author":"Wu","year":"2024","journal-title":"Lipids Heal. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhu, H., Wang, X., Lu, S., and Ou, K. (2023). Metabolic reprogramming of clear cell renal cell carcinoma. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1195500"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41585-022-00654-6","article-title":"Fatty acid metabolism reprogramming in ccRCC: Mechanisms and potential targets","volume":"20","author":"Tan","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Simeone, P., Tacconi, S., Longo, S., Lanuti, P., Bravaccini, S., Pirini, F., Ravaioli, S., Dini, L., and Giudetti, A.M. (2021). Expanding roles of de novo lipogenesis in breast cancer. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18073575"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xu, H., Chen, Y., Gu, M., Liu, C., Chen, Q., Zhan, M., and Wang, Z. (2021). Fatty acid metabolism reprogramming in advanced prostate cancer. Metabolites, 11.","DOI":"10.3390\/metabo11110765"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41573-021-00367-2","article-title":"Lipogenesis inhibitors: Therapeutic opportunities and challenges","volume":"21","author":"Batchuluun","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/14737159.2023.2195553","article-title":"The dark side of lipid metabolism in prostate and renal carcinoma: Novel insights into molecular diagnostic and biomarker discovery","volume":"23","author":"Lasorsa","year":"2023","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41420-025-02479-9","article-title":"The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma","volume":"11","author":"Zhang","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.metabol.2014.04.003","article-title":"De novo lipogenesis in health and disease","volume":"63","author":"Ameer","year":"2014","journal-title":"Metabolism"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Schulze","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.devcel.2021.04.013","article-title":"Lipid metabolism in cancer: New perspectives and emerging mechanisms","volume":"56","author":"Broadfield","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ccell.2014.12.002","article-title":"Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress","volume":"27","author":"Schug","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2013.05.017","article-title":"Cellular fatty acid metabolism and cancer","volume":"18","author":"Currie","year":"2013","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41586-019-0904-1","article-title":"Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity","volume":"566","author":"Vriens","year":"2019","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1051\/rnd:2005047","article-title":"Conversion of \u03b1-linolenic acid to longer-chain polyunsaturated fatty acids in human adults","volume":"45","author":"Burdge","year":"2005","journal-title":"Reprod. Nutr. Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13051","DOI":"10.1016\/S0021-9258(17)44078-6","article-title":"The polymerization of acetyl-CoA carboxylase","volume":"258","author":"Beaty","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1042\/BST0340223","article-title":"Regulation of acetyl-CoA carboxylase","volume":"34","author":"Brownsey","year":"2006","journal-title":"Biochem. Soc. Trans."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41594-019-0351-6","article-title":"Molecular basis for acetyl-CoA production by ATP-citrate lyase","volume":"27","author":"Wei","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1021\/bi992159y","article-title":"Phosphorylation of recombinant human ATP: Citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP: Citrate lyase by phosphorylated sugars","volume":"39","author":"Potapova","year":"2000","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/s42255-020-0245-2","article-title":"Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK \u03b21 isoforms","volume":"2","author":"Pinkosky","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e32656","DOI":"10.7554\/eLife.32656","article-title":"AMPK signaling to acetyl-CoA carboxylase is required for fasting-and cold-induced appetite but not thermogenesis","volume":"7","author":"Galic","year":"2018","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1194\/jlr.M500438-JLR200","article-title":"Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells","volume":"47","author":"Fediuc","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.cmet.2011.03.009","article-title":"AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice","volume":"13","author":"Li","year":"2011","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41586-018-0201-4","article-title":"Structural basis for regulation of human acetyl-CoA carboxylase","volume":"558","author":"Hunkeler","year":"2018","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eaai8596","DOI":"10.1126\/scisignal.aai8596","article-title":"Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2","volume":"10","author":"Viscarra","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"F271","DOI":"10.1152\/ajprenal.00221.2011","article-title":"Role of the USF1 transcription factor in diabetic kidney disease","volume":"301","author":"Sanchez","year":"2011","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28510","DOI":"10.1074\/jbc.M109.022244","article-title":"Hepatocyte growth factor family negatively regulates hepatic gluconeogenesis via induction of orphan nuclear receptor small heterodimer partner in primary hepatocytes","volume":"284","author":"Chanda","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1074\/jbc.M107895200","article-title":"Mechanism for fatty acid \u201csparing\u201d effect on glucose-induced transcription: Regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase","volume":"277","author":"Kawaguchi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"33895","DOI":"10.1074\/jbc.M204681200","article-title":"The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes","volume":"277","author":"Berwick","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8867","DOI":"10.1016\/S0021-9258(19)52474-7","article-title":"ATP-citrate lyase. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase","volume":"256","author":"Pierce","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.cmet.2018.04.015","article-title":"The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase","volume":"27","author":"White","year":"2018","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"51999","DOI":"10.1074\/jbc.M405522200","article-title":"Regulatory role of glycogen synthase kinase 3 for transcriptional activity of ADD1\/SREBP1c","volume":"279","author":"Kim","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cmet.2005.04.010","article-title":"Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCFFbw7","volume":"1","author":"Sundqvist","year":"2005","journal-title":"Cell Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4255","DOI":"10.1038\/s41467-019-12194-6","article-title":"Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis","volume":"10","author":"Kumari","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1074\/jbc.M112.397885","article-title":"Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2","volume":"288","author":"Yu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.biochi.2004.09.018","article-title":"SREBP transcription factors: Master regulators of lipid homeostasis","volume":"86","author":"Hegarty","year":"2004","journal-title":"Biochimie"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"26483","DOI":"10.1074\/jbc.M504041200","article-title":"Insig required for sterol-mediated inhibition of Scap\/SREBP binding to COPII proteins in vitro","volume":"280","author":"Sun","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13607","DOI":"10.1073\/pnas.201524598","article-title":"Decreased lipid synthesis in livers of mice with disrupted Site-1 protease gene","volume":"98","author":"Yang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cmet.2017.07.004","article-title":"Sweet sixteenth for ChREBP: Established roles and future goals","volume":"26","author":"Guilmeau","year":"2017","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1101\/gad.844900","article-title":"Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXR\u03b1 and LXR\u03b2","volume":"14","author":"Repa","year":"2000","journal-title":"Genes Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1194\/jlr.M600276-JLR200","article-title":"The mechanism mediating the activation of acetyl-coenzyme A carboxylase-\u03b1 gene transcription by the liver X receptor agonist T0-901317","volume":"47","author":"Talukdar","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11019","DOI":"10.1074\/jbc.M111041200","article-title":"Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors","volume":"277","author":"Joseph","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tem.2010.09.002","article-title":"Lipoexpediency: De novo lipogenesis as a metabolic signal transmitter","volume":"22","author":"Lodhi","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21466","DOI":"10.1074\/jbc.M110.209973","article-title":"Human SREBP1c expression in liver is directly regulated by peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1)","volume":"286","author":"Alvarez","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1194\/jlr.M600342-JLR200","article-title":"Coordinated control of bile acids and lipogenesis through FXR-dependent regulation of fatty acid synthase","volume":"47","author":"Matsukuma","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bbrc.2020.04.075","article-title":"Promotion of lipogenesis by PPAR\u03b3-activated FXR expression in adipocytes","volume":"527","author":"Shinohara","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.biocel.2012.01.003","article-title":"Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes","volume":"44","author":"Damiano","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"35392","DOI":"10.1074\/jbc.M405924200","article-title":"Platelet-derived growth factor stimulates membrane lipid synthesis through activation of phosphatidylinositol 3-kinase and sterol regulatory element-binding proteins","volume":"279","author":"Demoulin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.biochi.2010.08.001","article-title":"Hormonal and nutritional regulation of SCD1 gene expression","volume":"93","author":"Mauvoisin","year":"2011","journal-title":"Biochimie"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.febslet.2007.03.047","article-title":"T0901317 is a potent PXR ligand: Implications for the biology ascribed to LXR","volume":"581","author":"Mitro","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15013","DOI":"10.1074\/jbc.M511116200","article-title":"A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway","volume":"281","author":"Zhou","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1128\/IAI.73.8.4512-4521.2005","article-title":"A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria","volume":"73","author":"Georgel","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10555-021-09996-w","article-title":"Lipid metabolism reprogramming in renal cell carcinoma","volume":"41","author":"Heravi","year":"2022","journal-title":"Cancer Metastasis Rev."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tun, H.W., Marlow, L.A., von Roemeling, C.A., Cooper, S.J., Kreinest, P., Wu, K., Luxon, B.A., Sinha, M., Anastasiadis, P.Z., and Copland, J.A. (2010). Pathway signature and cellular differentiation in clear cell renal cell carcinoma. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010696"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature10602","article-title":"Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia","volume":"481","author":"Metallo","year":"2012","journal-title":"Nature"},{"key":"ref_70","first-page":"6967","article-title":"Overexpression of ATP citrate lyase in renal cell carcinoma tissues and its effect on the human renal carcinoma cells in vitro","volume":"15","author":"Teng","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102056","DOI":"10.1016\/j.tranon.2024.102056","article-title":"The prognostic value and its relationship with immune infiltration of ACLY in clear cell renal cell carcinoma","volume":"47","author":"Yin","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6599","DOI":"10.7150\/jca.33024","article-title":"The mRNA expression signature and prognostic analysis of multiple fatty acid metabolic enzymes in clear cell renal cell carcinoma","volume":"10","author":"Zhao","year":"2019","journal-title":"J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature12222","article-title":"Comprehensive molecular characterization of clear cell renal cell carcinoma","volume":"499","author":"Creighton","year":"2013","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.7150\/jca.26374","article-title":"TOFA induces cell cycle arrest and apoptosis in ACHN and 786-O cells through inhibiting PI3K\/Akt\/mTOR pathway","volume":"9","author":"He","year":"2018","journal-title":"J. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.juro.2008.04.135","article-title":"Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma","volume":"180","author":"Horiguchi","year":"2008","journal-title":"J. Urol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"153227","DOI":"10.1016\/j.prp.2020.153227","article-title":"Expression and prognostic significance of fatty acid synthase in clear cell renal cell carcinoma","volume":"216","author":"Yuan","year":"2020","journal-title":"Pathol.-Res. Pract."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xu, W., Hu, X., Anwaier, A., Wang, J., Liu, W., Tian, X., Zhu, W., Ma, C., Wan, F., and Shi, G. (2021). Fatty acid synthase correlates with prognosis-related abdominal adipose distribution and metabolic disorders of clear cell renal cell carcinoma. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.610229"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.juro.2008.03.186","article-title":"Pharmacological inhibitor of fatty acid synthase suppresses growth and invasiveness of renal cancer cells","volume":"180","author":"Horiguchi","year":"2008","journal-title":"J. Urol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, J., Xu, Y., Zhu, L., Zou, Y., Kong, W., Dong, B., Huang, J., Chen, Y., Xue, W., and Huang, Y. (2016). High expression of stearoyl-CoA desaturase 1 predicts poor prognosis in patients with clear-cell renal cell carcinoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166231"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1158\/1078-0432.CCR-12-3249","article-title":"Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma","volume":"19","author":"Marlow","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13166","DOI":"10.1111\/obr.13166","article-title":"The role of transcription factor 7-like 2 in metabolic disorders","volume":"22","author":"Zhang","year":"2021","journal-title":"Obes. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"0322","DOI":"10.34133\/research.0322","article-title":"HIF2\u03b1 promotes cancer metastasis through TCF7L2-dependent fatty acid synthesis in ccRCC","volume":"7","author":"Shi","year":"2024","journal-title":"Research"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Li, J., Bi, W., Lu, F., Pan, B., Xiong, M., Nasifu, L., Nie, Z., and He, B. (2023). Prognostic role of E2F1 gene expression in human cancer: A meta-analysis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10865-8"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.canlet.2021.05.012","article-title":"E2F1 promotes proliferation and metastasis of clear cell renal cell carcinoma via activation of SREBP1-dependent fatty acid biosynthesis","volume":"514","author":"Shen","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_85","first-page":"15","article-title":"Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells","volume":"707","author":"Gehrau","year":"2011","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/s41467-019-09116-x","article-title":"A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma","volume":"10","author":"Syafruddin","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.gde.2011.01.013","article-title":"Function and regulation of the Mediator complex","volume":"21","author":"Conaway","year":"2011","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/s41420-024-01944-1","article-title":"MED15 is upregulated by HIF-2\u03b1 and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis","volume":"10","author":"Hua","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.freeradbiomed.2014.01.018","article-title":"GPx8 peroxidase prevents leakage of H2O2 from the endoplasmic reticulum","volume":"70","author":"Ramming","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13046-023-02607-2","article-title":"GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT","volume":"42","author":"Nguyen","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"37602","DOI":"10.1074\/jbc.M111.284794","article-title":"Dual role of ancient ubiquitous protein 1 (AUP1) in lipid droplet accumulation and endoplasmic reticulum (ER) protein quality control","volume":"286","author":"Klemm","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1161\/ATVBAHA.117.309000","article-title":"AUP1 (ancient ubiquitous protein 1) is a key determinant of hepatic very-low\u2013density lipoprotein assembly and secretion","volume":"37","author":"Zhang","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1111\/cas.15445","article-title":"AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma","volume":"113","author":"Chen","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yun, H., Dumbell, R., Hanna, K., Bowen, J., McLean, S.L., Kantamneni, S., Pors, K., Wu, Q.-F., and Helfer, G. (2022). The chemerin-CMKLR1 axis is functionally important for central regulation of energy homeostasis. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.897105"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1158\/0008-5472.CAN-23-2926","article-title":"GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma","volume":"84","author":"Wang","year":"2024","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/jb\/mvs090","article-title":"The functional roles of S1P in immunity","volume":"152","author":"Hisano","year":"2012","journal-title":"J. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"154641","DOI":"10.1016\/j.prp.2023.154641","article-title":"Sphingosine kinase 1 regulates lipid metabolism to promote progression of kidney renal clear cell carcinoma","volume":"248","author":"Zhao","year":"2023","journal-title":"Pathol.-Res. Pract."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E1175","DOI":"10.1152\/ajpendo.00630.2012","article-title":"Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity","volume":"304","author":"Lackey","year":"2013","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1242\/dmm.008383","article-title":"Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease","volume":"5","author":"Friedrich","year":"2012","journal-title":"Dis. Models Mech."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/cac2.12413","article-title":"N6-methyladenosine-modified DBT alleviates lipid accumulation and inhibits tumor progression in clear cell renal cell carcinoma through the ANXA2\/YAP axis-regulated Hippo pathway","volume":"43","author":"Miao","year":"2023","journal-title":"Cancer Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/prot.21766","article-title":"Structure\u2013function relationships in the 2-oxo acid dehydrogenase family: Substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins","volume":"71","author":"Bunik","year":"2008","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41419-023-06090-7","article-title":"The m6A modification-mediated OGDHL exerts a tumor suppressor role in ccRCC by downregulating FASN to inhibit lipid synthesis and ERK signaling","volume":"14","author":"Shi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"116592","DOI":"10.1016\/j.lfs.2019.116592","article-title":"The recent insights into the function of ACAT1: A possible anti-cancer therapeutic target","volume":"232","author":"Goudarzi","year":"2019","journal-title":"Life Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"102043","DOI":"10.1016\/j.tranon.2024.102043","article-title":"ACAT1 suppresses clear cell renal cell carcinoma progression by AMPK mediated fatty acid metabolism","volume":"47","author":"Zheng","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"E772","DOI":"10.1152\/ajpendo.1999.277.4.E772","article-title":"Regulation of fatty acid oxidation of the heart by MCD and ACC during contractile stimulation","volume":"277","author":"Goodwin","year":"1999","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1158\/0008-5472.CAN-23-0969","article-title":"Fatty acid oxidation mediated by malonyl-CoA decarboxylase represses renal cell carcinoma progression","volume":"83","author":"Zhou","year":"2023","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.bbrc.2017.01.159","article-title":"HADHA, the alpha subunit of the mitochondrial trifunctional protein, is involved in long-chain fatty acid-induced autophagy in intestinal epithelial cells","volume":"484","author":"Maeyashiki","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"102112","DOI":"10.1016\/j.tranon.2024.102112","article-title":"HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis","volume":"49","author":"Chu","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"111558","DOI":"10.1016\/j.yexcr.2019.111558","article-title":"HADHA overexpression disrupts lipid metabolism and inhibits tumor growth in clear cell renal cell carcinoma","volume":"384","author":"Liu","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acs.chemrestox.8b00256","article-title":"Role of aldehyde dehydrogenases in physiopathological processes","volume":"32","author":"Calleja","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/s41419-024-06896-z","article-title":"N6-methyladenosine-modified ALDH9A1 modulates lipid accumulation and tumor progression in clear cell renal cell carcinoma through the NPM1\/IQGAP2\/AKT signaling pathway","volume":"15","author":"Tan","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1101\/gad.177444.111","article-title":"PR-Set7 and H4K20me1: At the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription","volume":"26","author":"Beck","year":"2012","journal-title":"Genes Dev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.canlet.2021.12.018","article-title":"SETD8 stabilized by USP17 epigenetically activates SREBP1 pathway to drive lipogenesis and oncogenesis of ccRCC","volume":"527","author":"Li","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/mc.23840","article-title":"The Mechanism of TRIM21 Inhibiting the Invasion and Migration of ccRCC by Stabilizing ASS1","volume":"64","author":"Yang","year":"2025","journal-title":"Mol. Carcinog."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13046-022-02583-z","article-title":"TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability","volume":"42","author":"Chen","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.molcel.2011.02.002","article-title":"Regulation of homologous recombination by RNF20-dependent H2B ubiquitination","volume":"41","author":"Nakamura","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/ncb1712","article-title":"Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells","volume":"10","author":"Minsky","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e00265-e17","DOI":"10.1128\/MCB.00265-17","article-title":"RNF20 suppresses tumorigenesis by inhibiting the SREBP1c-PTTG1 axis in kidney cancer","volume":"37","author":"Lee","year":"2017","journal-title":"Mol. Cell. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41556-024-01405-y","article-title":"LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth","volume":"26","author":"Li","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13046-017-0525-1","article-title":"Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma","volume":"36","author":"Du","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"614","DOI":"10.7150\/ijbs.103032","article-title":"HIF-2\u03b1\/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY","volume":"21","author":"Fei","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.18632\/oncotarget.13693","article-title":"Nuclear localization of the CK2\u03b1-subunit correlates with poor prognosis in clear cell renal cell carcinoma","volume":"8","author":"Rabjerg","year":"2016","journal-title":"Oncotarget"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1186\/s12935-024-03611-y","article-title":"Protein kinase CK2 sustains de novo fatty acid synthesis by regulating the expression of SCD-1 in human renal cancer cells","volume":"24","author":"Guerra","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.mito.2021.09.003","article-title":"Mitofusin 2: A link between mitochondrial function and substrate metabolism?","volume":"61","author":"Emery","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1111\/cas.16151","article-title":"MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma","volume":"115","author":"Cai","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1200\/JCO.2012.45.2003","article-title":"Molecular genetics of clear-cell renal cell carcinoma","volume":"32","author":"Brugarolas","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: Mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"Forbes","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"105070","DOI":"10.1016\/j.ebiom.2024.105070","article-title":"VHL mutation drives human clear cell renal cell carcinoma progression through PI3K\/AKT-dependent cholesteryl ester accumulation","volume":"103","author":"Zhang","year":"2024","journal-title":"EBioMedicine"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"154302","DOI":"10.1016\/j.metabol.2020.154302","article-title":"Ubiquitination of PPAR-gamma by pVHL inhibits ACLY expression and lipid metabolism, is implicated in tumor progression","volume":"110","author":"Noh","year":"2020","journal-title":"Metabolism"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13046-023-02940-6","article-title":"HIF-2\u03b1\/LINC02609\/APOL1-mediated lipid storage promotes endoplasmic reticulum homeostasis and regulates tumor progression in clear-cell renal cell carcinoma","volume":"43","author":"Xiao","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Mel\u00e9ndez-Rodr\u00edguez, F., Roche, O., Sanchez-Prieto, R., and Aragones, J. (2018). Hypoxia-inducible factor 2-dependent pathways driving Von Hippel\u2013Lindau-deficient renal cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00214"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1038\/s41467-017-01965-8","article-title":"HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism","volume":"8","author":"Du","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Chowdhury, B., Porter, E.G., Stewart, J.C., Ferreira, C.R., Schipma, M.J., and Dykhuizen, E.C. (2016). PBRM1 regulates the expression of genes involved in metabolism and cell adhesion in renal clear cell carcinoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153718"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1016\/j.celrep.2017.02.074","article-title":"The SWI\/SNF protein PBRM1 restrains VHL-loss-driven clear cell renal cell carcinoma","volume":"18","author":"Nargund","year":"2017","journal-title":"Cell Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"7572","DOI":"10.1038\/s41467-023-43378-w","article-title":"SETD2 deficiency accelerates sphingomyelin accumulation and promotes the development of renal cancer","volume":"14","author":"Rao","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_137","first-page":"331","article-title":"Loss of SETD2 induces a metabolic switch in renal cell carcinoma cell lines toward enhanced oxidative phosphorylation","volume":"18","author":"Liu","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"208","DOI":"10.53365\/nrfhh\/189500","article-title":"ATP-Citrate Lyase (ACLY): An extensive investigation from molecular insight to therapeutic implications","volume":"4","author":"Biju","year":"2024","journal-title":"Nat. Resour. Hum. Health"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e696","DOI":"10.1038\/cddis.2013.215","article-title":"ATP citrate lyase knockdown impacts cancer stem cells in vitro","volume":"4","author":"Hanai","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1101\/gad.283283.116","article-title":"Cullin3\u2013KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression","volume":"30","author":"Zhang","year":"2016","journal-title":"Genes Dev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1111\/jcmm.16235","article-title":"ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p-eIF2\u03b1\/ATF4\/CHOP axis","volume":"25","author":"Zheng","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"43713","DOI":"10.18632\/oncotarget.9666","article-title":"Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism","volume":"7","author":"Shah","year":"2016","journal-title":"Oncotarget"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/hep.31249","article-title":"The IKK\u03b2-USP30-ACLY axis controls lipogenesis and tumorigenesis","volume":"73","author":"Gu","year":"2021","journal-title":"Hepatology"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"117510","DOI":"10.1016\/j.biopha.2024.117510","article-title":"Morusin, a novel inhibitor of ACLY, induces mitochondrial apoptosis in hepatocellular carcinoma cells through ROS-mediated mitophagy","volume":"180","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ccr.2005.09.008","article-title":"ATP citrate lyase inhibition can suppress tumor cell growth","volume":"8","author":"Hatzivassiliou","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nm.4181","article-title":"Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models","volume":"22","author":"Svensson","year":"2016","journal-title":"Nat. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.bbrc.2009.05.045","article-title":"Acetyl-CoA carboxylase-\u03b1 inhibitor TOFA induces human cancer cell apoptosis","volume":"385","author":"Wang","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3892\/mmr.2013.1505","article-title":"TOFA suppresses ovarian cancer cell growth in vitro and in vivo","volume":"8","author":"Li","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.cmet.2018.08.020","article-title":"Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma","volume":"29","author":"Lally","year":"2019","journal-title":"Cell Metab."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"P5-17-01","DOI":"10.1158\/1538-7445.SABCS21-P5-17-01","article-title":"Abstract P5-17-01: Targeting Acetyl-CoA carboxylase in pre-clinical breast cancer models","volume":"82","author":"Foldi","year":"2022","journal-title":"Cancer Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12032-025-02697-2","article-title":"Fatty acid synthase inhibitor cerulenin attenuates glioblastoma progression by reducing EMT and stemness phenotypes, inducing oxidative and ER stress response, and targeting PI3K\/AKT\/NF-\u03baB axis","volume":"42","author":"Pekmez","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"100660","DOI":"10.1016\/j.jlr.2024.100660","article-title":"Fatty acid synthase inhibitor cerulenin hinders liver cancer stem cell properties through FASN\/APP axis as novel therapeutic strategies","volume":"65","author":"Chen","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/s41419-022-04926-2","article-title":"FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis","volume":"13","author":"Du","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41419-026-08481-y","article-title":"Targeting fatty acid synthase suppresses tumor development in NF2\/CDKN2A-deficient malignant pleural mesothelioma","volume":"17","author":"Karnan","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1667\/RR14173.1","article-title":"Inhibition of fatty acid synthase sensitizes prostate cancer cells to radiotherapy","volume":"184","author":"Rae","year":"2015","journal-title":"Radiat. Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.biopha.2007.08.020","article-title":"Fatty acid synthase inhibitors cerulenin and C75 retard growth and induce caspase-dependent apoptosis in human melanoma A-375 cells","volume":"61","author":"Ho","year":"2007","journal-title":"Biomed. Pharmacother."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"175456","DOI":"10.1016\/j.ejphar.2022.175456","article-title":"Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells","volume":"939","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2217\/nnm.15.193","article-title":"Orlistat and antisense-miRNA-loaded PLGA-PEG nanoparticles for enhanced triple negative breast cancer therapy","volume":"11","author":"Foygel","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1158\/1535-7163.MCT-15-0579","article-title":"Folate receptor\u2013targeted polymeric micellar nanocarriers for delivery of orlistat as a repurposed drug against triple-negative breast cancer","volume":"15","author":"Paulmurugan","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s43018-021-00183-y","article-title":"Fatty acid synthesis is required for breast cancer brain metastasis","volume":"2","author":"Ferraro","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3768","DOI":"10.1016\/j.bmc.2017.05.016","article-title":"Discovery of novel and potent stearoyl coenzyme A desaturase 1 (SCD1) inhibitors as anticancer agents","volume":"25","author":"Imamura","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40170-025-00375-5","article-title":"CD36 inhibition enhances the anti-proliferative effects of PI3K inhibitors in PTEN-loss anti-HER2 resistant breast cancer cells","volume":"13","author":"Liu","year":"2025","journal-title":"Cancer Metab."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s11306-024-02179-y","article-title":"Combination of low glucose and SCD1 inhibition impairs cancer metabolic plasticity and growth in MCF-7 cancer cells: A comprehensive metabolomic and lipidomic analysis","volume":"20","author":"Zhu","year":"2024","journal-title":"Metabolomics"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/s12935-024-03540-w","article-title":"Stearoyl CoA desaturase inhibition can effectively induce apoptosis in bladder cancer stem cells","volume":"24","author":"Li","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Basappa, J., ElAzzouny, M.A., Rolland, D.C., Sahasrabuddhe, A.A., Ma, K., Bazilevsky, G.A., Hwang, S.R., Basrur, V., Conlon, K.P., and Bailey, N.G. (2020). Tyrosine phosphorylation is critical for ACLY activity in lipid metabolism and cancer. bioRxiv.","DOI":"10.1101\/2020.01.20.910752"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"100797","DOI":"10.1016\/j.eclinm.2021.100797","article-title":"First-in-human study of the safety, pharmacokinetics, and pharmacodynamics of first-in-class fatty acid synthase inhibitor TVB-2640 alone and with a taxane in advanced tumors","volume":"34","author":"Falchook","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"TPS248","DOI":"10.1200\/JCO.2024.42.4_suppl.TPS248","article-title":"A phase I, open-label, dose-finding study of fatty acid synthase (FASN) inhibitor TVB-2640 administered in combination with enzalutamide (Enza) in men with metastatic castration-resistant prostate cancer (mCRPC)","volume":"42","author":"Nuzzo","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41586-025-09297-0","article-title":"ACLY inhibition promotes tumour immunity and suppresses liver cancer","volume":"645","author":"Gautam","year":"2025","journal-title":"Nature"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"eadi2465","DOI":"10.1126\/sciadv.adi2465","article-title":"Inhibition of ACLY overcomes cancer immunotherapy resistance via polyunsaturated fatty acids peroxidation and cGAS-STING activation","volume":"9","author":"Xiang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_170","first-page":"1230","article-title":"Activation of HIF-1\u03b1\/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation","volume":"52","author":"Ma","year":"2023","journal-title":"Chin. J. Pathol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s12943-025-02457-w","article-title":"Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: Metabolic vulnerabilities and therapeutic targeting","volume":"24","author":"Deng","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Chen, D., and Hua, C. (2025). HIF-2\u03b1 inhibitors in clear cell renal cell carcinoma: A clinical pharmacy perspective on lipid metabolism, therapeutic management, and resistance strategies. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1735808"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"102513","DOI":"10.1016\/j.tranon.2025.102513","article-title":"Lipid metabolism of clear cell renal cell carcinoma predicts survival and affects intratumoral CD8 T cells","volume":"61","author":"Simeth","year":"2025","journal-title":"Transl. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"551","DOI":"10.2217\/fon.10.11","article-title":"Fatty acid synthase as a potential therapeutic target in cancer","volume":"6","author":"Flavin","year":"2010","journal-title":"Future Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2174\/157489212799972891","article-title":"Anti-cancer drugs targeting fatty acid synthase (FAS)","volume":"7","author":"Pandey","year":"2012","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10555-024-10170-1","article-title":"Lipid metabolism and its implications in tumor cell plasticity and drug resistance: What we learned thus far?","volume":"43","author":"Vishwa","year":"2024","journal-title":"Cancer Metastasis Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4924\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:54:18Z","timestamp":1780404858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":176,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114924"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114924","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}