{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:11:37Z","timestamp":1764785497404,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NATL INST OF HLTH NCATS","award":["R21TR003044","AWD14553"],"award-info":[{"award-number":["R21TR003044","AWD14553"]}]},{"name":"SDHB PHEO PARA COALITION","award":["R21TR003044","AWD14553"],"award-info":[{"award-number":["R21TR003044","AWD14553"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B (SDHB) gene are susceptible to the development of PPGL. A physiologically relevant PCC patient-derived cell line hPheo1 was developed, and SDHB_KD cells carrying a stable short hairpin knockdown of SDHB were derived from it. An untargeted metabolomic approach uncovered an overactive polyamine pathway in the SDHB_KD cells that was subsequently fully validated in a large set of human SDHB-mutant PPGL tumor samples. We previously reported that treatment with the polyamine metabolism inhibitor N1,N11-diethylnorspermine (DENSPM) drastically inhibited growth of these PCC-derived cells in culture as well as in xenograft mouse models. Here we explored the mechanisms underlying DENSPM action in hPheo1 and SDHB_KD cells. Specifically, by performing an RNAseq analysis, we have identified gene expression changes associated with DENSPM treatment that broadly interfere with all aspects of lipid metabolism, including fatty acid (FA) synthesis, desaturation, and import\/uptake. Furthermore, by performing an untargeted lipidomic liquid chromatography\u2013mass spectrometry (LC\/MS)-based analysis we uncovered specific groups of lipids that are dramatically reduced as a result of DENSPM treatment. Specifically, the bulk of plasmanyl ether lipid species that have been recently reported as the major determinants of cancer cell fate are notably decreased. In summary, this work suggests an intersection between active polyamine and lipid pathways in PCC cells.<\/jats:p>","DOI":"10.3390\/ijms251810029","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T09:43:13Z","timestamp":1726652593000},"page":"10029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polyamine Pathway Inhibitor DENSPM Suppresses Lipid Metabolism in Pheochromocytoma Cell Line"],"prefix":"10.3390","volume":"25","author":[{"given":"Hans K.","family":"Ghayee","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, College of Medicine, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaylie A.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiling","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, College of Medicine, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-4688","authenticated-orcid":false,"given":"Heather M.","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateo","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby C.","family":"Straight","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, College of Medicine, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL 32608, USA"},{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-8795","authenticated-orcid":false,"given":"Fahong","family":"Yu","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-1968","authenticated-orcid":false,"given":"Fatima","family":"Smagulova","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Rennes, EHESP, Inserm, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Campus Sante de Villejean\u2014UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei G.","family":"Tevosian","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 03610, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.ecl.2019.08.006","article-title":"Pheochromocytomas and Paragangliomas","volume":"48","author":"Tevosian","year":"2019","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S2213-8587(23)00038-4","article-title":"Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants","volume":"11","author":"Wanna","year":"2023","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s12022-022-09704-6","article-title":"Overview of the 2022 WHO Classification of Paragangliomas and Pheochromocytomas","volume":"33","author":"Mete","year":"2022","journal-title":"Endocr. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccell.2017.01.001","article-title":"Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma","volume":"31","author":"Fishbein","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1530\/EO-22-0044","article-title":"Pheochromocytoma and paraganglioma: Germline genetics and hereditary syndromes","volume":"2","author":"Turin","year":"2022","journal-title":"Endocr. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ghayee, H.K., Bhagwandin, V.J., Stastny, V., Click, A., Ding, L.-H., Mizrachi, D., Zou, Y.S., Chari, R., Lam, W.L., and Bachoo, R.M. (2013). Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065624"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"154297","DOI":"10.1016\/j.metabol.2020.154297","article-title":"Targeting pheochromocytoma\/paraganglioma with polyamine inhibitors","volume":"110","author":"Rai","year":"2020","journal-title":"Metabolism"},{"key":"ref_8","first-page":"7754","article-title":"Polyamine depletion in human melanoma cells leads to G1 arrest associated with induction of p21WAF1\/CIP1\/SDI1, changes in the expression of p21-regulated genes, and a senescence-like phenotype","volume":"61","author":"Kramer","year":"2001","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41568-018-0050-3","article-title":"Polyamine metabolism and cancer: Treatments, challenges and opportunities","volume":"18","author":"Casero","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1186\/s12935-020-01545-9","article-title":"Polyamines and related signaling pathways in cancer","volume":"20","author":"Li","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1038\/s41467-021-20896-z","article-title":"Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas","volume":"12","author":"Khan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaau1099","DOI":"10.1126\/scitranslmed.aau1099","article-title":"Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma","volume":"11","author":"Gamble","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1038\/s41467-024-46776-w","article-title":"Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer","volume":"15","author":"Bi","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41586-023-05891-2","article-title":"Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer","volume":"616","author":"Lee","year":"2023","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cmet.2019.11.010","article-title":"Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer","volume":"31","author":"Snaebjornsson","year":"2020","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101529","DOI":"10.1016\/j.molmet.2022.101529","article-title":"New dawn for cancer cell death: Emerging role of lipid metabolism","volume":"63","author":"Zhang","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s12011-019-01699-2","article-title":"Sodium Orthovanadate Changes Fatty Acid Composition and Increased Expression of Stearoyl-Coenzyme A Desaturase in THP-1 Macrophages","volume":"193","author":"Korbecki","year":"2019","journal-title":"Biol. Trace Element Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/cas.12108","article-title":"Positive feedback loop and synergistic effects between hypoxia-inducible factor-2alpha and stearoyl-CoA desaturase-1 promote tumorigenesis in clear cell renal cell carcinoma","volume":"104","author":"Zhang","year":"2013","journal-title":"Cancer Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.bbrc.2017.11.163","article-title":"SREBP1-driven lipid desaturation supports clear cell renal cell carcinoma growth through regulation of NF-kappaB signaling","volume":"495","author":"Yang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.21037\/tcr-22-431","article-title":"Histone methyltransferase KMT2D mediated lipid metabolism via peroxisome proliferator-activated receptor gamma in prostate cancer","volume":"11","author":"Zhai","year":"2022","journal-title":"Transl. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s13046-018-0852-x","article-title":"RBM38 plays a tumor-suppressor role via stabilizing the p53-mdm2 loop function in hepatocellular carcinoma","volume":"37","author":"Ye","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.surg.2021.04.049","article-title":"Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics","volume":"171","author":"Subramanian","year":"2021","journal-title":"Surgery"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151912","DOI":"10.1016\/j.acthis.2022.151912","article-title":"Human adrenocortical carcinoma cell line (NCI-H295R): An in vitro screening model for the assessment of endocrine disruptors\u2019 actions on steroidogenesis with an emphasis on cell ultrastructural features","volume":"124","author":"Duranova","year":"2022","journal-title":"Acta Histochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"bqac102","DOI":"10.1210\/endocr\/bqac102","article-title":"Mitotane Targets Lipid Droplets to Induce Lipolysis in Adrenocortical Carcinoma","volume":"163","author":"Warde","year":"2022","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"bqad003","DOI":"10.1210\/endocr\/bqad003","article-title":"Targeting of a New Node in Lipid Metabolism as a Potential Treatment Strategy for ACC","volume":"164","author":"LaPensee","year":"2023","journal-title":"Endocrinology"},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.cmet.2022.09.023","article-title":"The role of lipids in cancer progression and metastasis","volume":"34","author":"Bigas","year":"2022","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s43018-023-00513-2","article-title":"A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-kappaB signaling","volume":"4","author":"Doglioni","year":"2023","journal-title":"Nat. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1158\/0008-5472.CAN-07-5616","article-title":"Effect of Low-Fat Diet on Development of Prostate Cancer and Akt Phosphorylation in the Hi-Myc Transgenic Mouse Model","volume":"68","author":"Kobayashi","year":"2008","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1038\/s41467-019-12298-z","article-title":"High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program","volume":"10","author":"Zadra","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/BST20140249","article-title":"Wnt acylation and its functional implication in Wnt signalling regulation","volume":"43","author":"Janda","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1080\/09687680802649582","article-title":"Ras acylation, compartmentalization and signaling nanoclusters (Review)","volume":"26","author":"Henis","year":"2009","journal-title":"Mol. Membr. Biol."},{"key":"ref_33","first-page":"435","article-title":"Lipid Droplets and the Management of Cellular Stress","volume":"92","author":"Jarc","year":"2019","journal-title":"Yale J. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nm.4409","article-title":"Cancer stem cells revisited","volume":"23","author":"Batlle","year":"2017","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.biochi.2022.07.008","article-title":"Serum fatty acid profiling in patients with SDHx mutations: New advances on cellular metabolism in SDH deficiency","volume":"201","author":"Vamecq","year":"2022","journal-title":"Biochimie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.2337\/db21-0834","article-title":"Beta-Cell Succinate Dehydrogenase Deficiency Triggers Metabolic Dysfunction and Insulinopenic Diabetes","volume":"71","author":"Lee","year":"2022","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eabm8161","DOI":"10.1126\/sciimmunol.abm8161","article-title":"Succinate dehydrogenase\/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation","volume":"7","author":"Chen","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nastasi, C., Willerlev-Olsen, A., Dalhoff, K., Ford, S.L., Gadsb\u00f8ll, A.-S., Buus, T.B., Gluud, M., Danielsen, M., Litman, T., and Bonefeld, C.M. (2021). Inhibition of succinate dehydrogenase activity impairs human T cell activation and function. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80933-7"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1016\/j.cell.2021.06.007","article-title":"Polyamine metabolism is a central determinant of helper T cell lineage fidelity","volume":"184","author":"Puleston","year":"2021","journal-title":"Cell"},{"key":"ref_41","first-page":"811","article-title":"Polyamines instruct T-cell differentiation","volume":"23","author":"Wang","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1016\/j.cell.2021.05.045","article-title":"Metabolic modeling of single Th17 cells reveals regulators of autoimmunity","volume":"184","author":"Wagner","year":"2021","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/nrc2222","article-title":"Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis","volume":"7","author":"Menendez","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","first-page":"27","article-title":"Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro","volume":"13","author":"Medes","year":"1953","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R146","DOI":"10.1152\/ajpregu.1984.247.1.R146","article-title":"Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor","volume":"247","author":"Ookhtens","year":"1984","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/01.mco.0000232894.28674.30","article-title":"Increased lipogenesis in cancer cells: New players, novel targets","volume":"9","author":"Swinnen","year":"2006","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40880-018-0301-4","article-title":"Lipid metabolism reprogramming and its potential targets in cancer","volume":"38","author":"Cheng","year":"2018","journal-title":"Cancer Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1111\/febs.13681","article-title":"Lipid desaturation\u2014The next step in targeting lipogenesis in cancer?","volume":"283","author":"Peck","year":"2016","journal-title":"FEBS J."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/MCO.0000000000000601","article-title":"Dealing with saturated and unsaturated fatty acid metabolism for anticancer therapy","volume":"22","author":"Dierge","year":"2019","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/MCO.0000000000000381","article-title":"Emerging roles of lipid metabolism in cancer progression","volume":"20","author":"Corbet","year":"2017","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Fhu, C.W., and Ali, A. (2020). Fatty Acid Synthase: An Emerging Target in Cancer. Molecules, 25.","DOI":"10.3390\/molecules25173935"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1080\/14728222.2017.1381087","article-title":"Fatty acid synthase (FASN) as a therapeutic target in breast cancer","volume":"21","author":"Menendez","year":"2017","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biochi.2020.08.020","article-title":"Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors","volume":"178","author":"Dierge","year":"2020","journal-title":"Biochimie"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eabd7459","DOI":"10.1126\/sciadv.abd7459","article-title":"Mechanisms of stearoyl CoA desaturase inhibitor sensitivity and acquired resistance in cancer","volume":"7","author":"Oatman","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Guo, Z., Bergeron, K.-F., Lingrand, M., and Mounier, C. (2023). Unveiling the MUFA\u2013Cancer Connection: Insights from Endogenous and Exogenous Perspectives. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129921"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Morais, C.M., Cardoso, A.M., Ara\u00fajo, A.R.D., Reis, A., Domingues, P., Domingues, M.R.M., de Lima, M.C.P., and Jurado, A.S. (2022). Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113014"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Parik, S., Fern\u00e1ndez-Garc\u00eda, J., Lodi, F., De Vlaminck, K., Derweduwe, M., De Vleeschouwer, S., Sciot, R., Geens, W., Weng, L., and Bosisio, F.M. (2022). GBM tumors are heterogeneous in their fatty acid metabolism and modulating fatty acid metabolism sensitizes cancer cells derived from recurring GBM tumors to temozolomide. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.988872"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39970","DOI":"10.18632\/oncotarget.9461","article-title":"SCD1 is associated with tumor promotion, late stage and poor survival in lung adenocarcinoma","volume":"7","author":"Huang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12935-019-0809-y","article-title":"SCD1 is required for EGFR-targeting cancer therapy of lung cancer via re-activation of EGFR\/PI3K\/AKT signals","volume":"19","author":"She","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1158\/1541-7786.MCR-18-0199","article-title":"De. Novo Fatty Acid Synthesis-Driven Sphingolipid Metabolism Promotes Metastatic Potential of Colorectal Cancer","volume":"17","author":"Jafari","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5355","DOI":"10.1158\/0008-5472.CAN-19-0369","article-title":"Stearoyl-CoA Desaturase 1 Protects Ovarian Cancer Cells from Ferroptotic Cell Death","volume":"79","author":"Tesfay","year":"2019","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"107806","DOI":"10.1016\/j.celrep.2020.107806","article-title":"mTOR Signaling and SREBP Activity Increase FADS2 Expression and Can Activate Sapienate Biosynthesis","volume":"31","author":"Triki","year":"2020","journal-title":"Cell Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/s41416-019-0451-4","article-title":"Lipid metabolism in cancer cells under metabolic stress","volume":"120","author":"Munir","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8882","DOI":"10.1073\/pnas.1307237110","article-title":"Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids","volume":"110","author":"Kamphorst","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.celrep.2014.08.056","article-title":"Fatty Acid Uptake and Lipid Storage Induced by HIF-1\u03b1 Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation","volume":"9","author":"Bensaad","year":"2014","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1038\/onc.2014.439","article-title":"SREBP maintains lipid biosynthesis and viability of cancer cells under lipid- and oxygen-deprived conditions and defines a gene signature associated with poor survival in glioblastoma multiforme","volume":"34","author":"Lewis","year":"2015","journal-title":"Oncogene"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1038\/s41467-018-04987-y","article-title":"FABP4 as a key determinant of metastatic potential of ovarian cancer","volume":"9","author":"Gharpure","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6462","DOI":"10.1038\/onc.2017.247","article-title":"Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia","volume":"36","author":"Gallagher","year":"2017","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/bjh.16853","article-title":"Low-density lipoprotein receptor (LDLR) is an independent adverse prognostic factor in acute myeloid leukaemia","volume":"192","author":"Floeth","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Gonias, S.L., Karimi-Mostowfi, N., Murray, S.S., Mantuano, E., and Gilder, A.S. (2017). Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186649"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1073\/pnas.1421601112","article-title":"Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma","volume":"112","author":"Guillaumond","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.cmet.2015.03.002","article-title":"Uncoupling Nuclear Receptor LXR and Cholesterol Metabolism in Cancer","volume":"21","author":"Bovenga","year":"2015","journal-title":"Cell Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature20791","article-title":"Targeting metastasis-initiating cells through the fatty acid receptor CD36","volume":"541","author":"Pascual","year":"2017","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1096\/fj.202000052R","article-title":"SREBP1 regulates mitochondrial metabolism in oncogenic KRAS expressing NSCLC","volume":"34","author":"Ruiz","year":"2020","journal-title":"FASEB J."},{"key":"ref_77","first-page":"251","article-title":"Alkyl and alk-1-enyl ethers of glycerol in lipids from normal and neoplastic human tissues","volume":"29","author":"Snyder","year":"1969","journal-title":"Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14912","DOI":"10.1073\/pnas.1310894110","article-title":"Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity","volume":"110","author":"Benjamin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","unstructured":"Henry, W.S., M\u00fcller, S., Yang, J.S., Innes-Gold, S., Das, S., Reinhardt, F., Sigmund, K., Phadnis, V.V., Wan, Z., and Eaton, E. Ether lipids influence cancer cell fate by modulating iron uptake. bioRxiv."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2106947118","DOI":"10.1073\/pnas.2106947118","article-title":"Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer","volume":"118","author":"Aggarwal","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101936","DOI":"10.1016\/j.molmet.2024.101936","article-title":"Roles and therapeutic targeting of ceramide metabolism in cancer","volume":"83","author":"Wajapeyee","year":"2024","journal-title":"Mol. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Canals, D., and Hannun, Y.A. (2024). Biological function, topology, and quantification of plasma membrane Ceramide. Adv. Biol. Regul., 91.","DOI":"10.1016\/j.jbior.2023.101009"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"27855","DOI":"10.1074\/jbc.R111.254359","article-title":"Many ceramides","volume":"286","author":"Hannun","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0962-8924(99)01694-3","article-title":"Ceramide in the eukaryotic stress response","volume":"10","author":"Hannun","year":"2000","journal-title":"Trends Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/sj.leu.2402197","article-title":"Ceramide regulates cellular homeostasis via diverse stress signaling pathways","volume":"15","author":"Ruvolo","year":"2001","journal-title":"Leukemia"},{"key":"ref_86","first-page":"114","article-title":"Ceramide in apoptosis: An overview and current perspectives","volume":"1585","author":"Pettus","year":"2002","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"24154","DOI":"10.1074\/jbc.272.39.24154","article-title":"Direct Inhibition of Mitochondrial Respiratory Chain Complex III by Cell-permeable Ceramide","volume":"272","author":"Gudz","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.2174\/092986709788682182","article-title":"Inhibition of Sphingomyelin Hydrolysis: Targeting the Lipid Mediator Ceramide as a Key Regulator of Cellular Fate","volume":"16","author":"Claus","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1007\/s13361-017-1608-0","article-title":"Expanding Lipidome Coverage Using LC-MS\/MS Data-Dependent Acquisition with Automated Exclusion List Generation","volume":"28","author":"Koelmel","year":"2017","journal-title":"J. Am. Soc. Mass. Spectrom."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Koelmel, J.P., Kroeger, N.M., Ulmer, C.Z., Bowden, J.A., Patterson, R.E., Cochran, J.A., Beecher, C.W.W., Garrett, T.J., and Yost, R.A. (2017). LipidMatch: An automated workflow for rule-based lipid identification using untargeted high-resolution tandem mass spectrometry data. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1744-3"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"171","DOI":"10.7150\/ijbs.7357","article-title":"Fatty acid synthase mediates the epithelial-mesenchymal transition of breast cancer cells","volume":"10","author":"Li","year":"2014","journal-title":"Int. J. Biol. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Veprik, A., Denwood, G., Liu, D., Bany Bakar, R., Morfin, V., McHugh, K., Tebeka, N.N., Vetterli, L., Yonova-Doing, E., and Gribble, F. (2022). Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03170-w"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kolahi, K., Louey, S., Varlamov, O., and Thornburg, K. (2016). Real-Time Tracking of BODIPY-C12 Long-Chain Fatty Acid in Human Term Placenta Reveals Unique Lipid Dynamics in Cytotrophoblast Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153522"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1002\/1878-0261.12816","article-title":"Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer","volume":"14","author":"Merino","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/s41431-019-0414-5","article-title":"Splice-site variant in ACSL5: A marker promoting opposing effect on cell viability and protein expression","volume":"27","author":"Karaky","year":"2019","journal-title":"Eur. J. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10029\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:58:22Z","timestamp":1760111902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/10029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":96,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms251810029"],"URL":"https:\/\/doi.org\/10.3390\/ijms251810029","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,9,18]]}}}