Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells.
Apoptosis
ER stress
Lipid metabolism
Ovarian cancer
SCD1
Journal
Journal of ovarian research
ISSN: 1757-2215
Titre abrégé: J Ovarian Res
Pays: England
ID NLM: 101474849
Informations de publication
Date de publication:
02 Apr 2024
02 Apr 2024
Historique:
received:
30
11
2023
accepted:
13
03
2024
medline:
3
4
2024
pubmed:
3
4
2024
entrez:
2
4
2024
Statut:
epublish
Résumé
Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.
Identifiants
pubmed: 38566208
doi: 10.1186/s13048-024-01389-1
pii: 10.1186/s13048-024-01389-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73Subventions
Organisme : Korea Health Technology R&D Project
ID : HI16C2037
Organisme : Korea Health Technology R&D Project
ID : HI16C2037
Organisme : Korea Health Technology R&D Project
ID : HI16C2037
Organisme : Korea Health Technology R&D Project
ID : HI16C2037
Organisme : Korea Foundation for Cancer Research
ID : CB-2022-A-2
Organisme : Korea Foundation for Cancer Research
ID : CB-2022-A-2
Organisme : Korea Foundation for Cancer Research
ID : CB-2022-A-2
Organisme : Korea Foundation for Cancer Research
ID : CB-2022-A-2
Informations de copyright
© 2024. The Author(s).
Références
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.
pubmed: 36633525
doi: 10.3322/caac.21763
Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers. 2016;2:16061.
pubmed: 27558151
pmcid: 7290868
doi: 10.1038/nrdp.2016.61
Desai A, Xu J, Aysola K, Qin Y, Okoli C, Hariprasad R, et al. Epithelial ovarian cancer: an overview. World J Transl Med. 2014;3(1):1–8.
pubmed: 25525571
pmcid: 4267287
doi: 10.5528/wjtm.v3.i1.1
Bonifácio VDB. Ovarian Cancer biomarkers: moving Forward in early detection. Adv Exp Med Biol. 2020;1219:355–63.
pubmed: 32130708
doi: 10.1007/978-3-030-34025-4_18
Sant M, Aareleid T, Berrino F, Lasota MB, Carli P, Faivre J, et al. EUROCARE-3: survival of cancer patients diagnosed 1990–94—results and commentary. Ann Oncol. 2003;14:v61–118.
pubmed: 14684501
doi: 10.1093/annonc/mdg754
Martínez-Reyes I, Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer. 2021;21(10):669–80.
pubmed: 34272515
doi: 10.1038/s41568-021-00378-6
Pavlova Natalya N, Thompson Craig B. The emerging Hallmarks of Cancer Metabolism. Cell Metabol. 2016;23(1):27–47.
doi: 10.1016/j.cmet.2015.12.006
Wu W, Zhao S. Metabolic changes in cancer: beyond the Warburg effect. Acta Biochim Biophys Sin. 2013;45(1):18–26.
pubmed: 23257292
doi: 10.1093/abbs/gms104
Munir R, Lisec J, Swinnen JV, Zaidi N. Lipid metabolism in cancer cells under metabolic stress. Br J Cancer. 2019;120(12):1090–8.
pubmed: 31092908
pmcid: 6738079
doi: 10.1038/s41416-019-0451-4
Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4–22.
pubmed: 31819192
doi: 10.1038/s41416-019-0650-z
Baenke F, Peck B, Miess H, Schulze A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 2013;6(6):1353–63.
pubmed: 24203995
pmcid: 3820259
doi: 10.1242/dmm.011338
Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the Wheels of the Cancer machine: the role of lipid metabolism in Cancer. Cell Metabol. 2020;31(1):62–76.
doi: 10.1016/j.cmet.2019.11.010
Vasseur S, Guillaumond F. Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance. Oncogenesis. 2022;11(1):46.
pubmed: 35945203
pmcid: 9363460
doi: 10.1038/s41389-022-00420-8
Mashima T, Seimiya H, Tsuruo T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer. 2009;100(9):1369–72.
pubmed: 19352381
pmcid: 2694429
doi: 10.1038/sj.bjc.6605007
Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res. 2013;52(4):585–9.
pubmed: 24001676
pmcid: 4002264
doi: 10.1016/j.plipres.2013.08.005
Fernández LP, Gómez de Cedrón M, Ramírez de Molina A. Alterations of lipid metabolism in Cancer: implications in prognosis and treatment. Front Oncol. 2020;10:2144.
doi: 10.3389/fonc.2020.577420
Dobrzyn P, Dobrzyn A, Miyazaki M, Cohen P, Asilmaz E, Hardie DG, et al. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci USA. 2004;101(17):6409–14.
pubmed: 15096593
pmcid: 404058
doi: 10.1073/pnas.0401627101
Ide Y, Waki M, Hayasaka T, Nishio T, Morita Y, Tanaka H, et al. Human breast cancer tissues contain abundant phosphatidylcholine(36∶1) with high stearoyl-CoA desaturase-1 expression. PLoS ONE. 2013;8(4):e61204.
pubmed: 23613812
pmcid: 3629004
doi: 10.1371/journal.pone.0061204
Huang J, Fan X-X, He J, Pan H, Li R-Z, Huang L, et al. SCD1 is associated with tumor promotion, late stage and poor survival in lung adenocarcinoma. Oncotarget. 2016;7(26):39970–9.
pubmed: 27223066
pmcid: 5129985
doi: 10.18632/oncotarget.9461
Huang G-M, Jiang Q-H, Cai C, Qu M, Shen W. SCD1 negatively regulates autophagy-induced cell death in human hepatocellular carcinoma through inactivation of the AMPK signaling pathway. Cancer Lett. 2015;358(2):180–90.
pubmed: 25528629
doi: 10.1016/j.canlet.2014.12.036
Roongta UV, Pabalan JG, Wang X, Ryseck RP, Fargnoli J, Henley BJ, et al. Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy. Mol Cancer Res. 2011;9(11):1551–61.
pubmed: 21954435
doi: 10.1158/1541-7786.MCR-11-0126
Li J, Ding SF, Habib NA, Fermor BF, Wood CB, Gilmour RS. Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues. Int J Cancer. 1994;57(3):348–52.
pubmed: 7909540
doi: 10.1002/ijc.2910570310
Chen L, Ren J, Yang L, Li Y, Fu J, Li Y, et al. Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis. Sci Rep. 2016;6:19665.
pubmed: 26813308
pmcid: 4728559
doi: 10.1038/srep19665
Wang W, Cho U, Yoo A, Jung C-L, Kim B, Kim H et al. Wnt/β-Catenin inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer. Front Oncol. 2022;12.
Han Y, Kim B, Cho U, Park IS, Kim SI, Dhanasekaran DN, et al. Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells. Oncogene. 2019;38(45):7089–105.
pubmed: 31409904
doi: 10.1038/s41388-019-0949-5
Ascenzi F, De Vitis C, Maugeri-Saccà M, Napoli C, Ciliberto G, Mancini R. SCD1, autophagy and cancer: implications for therapy. J Exp Clin Cancer Res. 2021;40(1):265.
pubmed: 34429143
pmcid: 8383407
doi: 10.1186/s13046-021-02067-6
Ariyama H, Kono N, Matsuda S, Inoue T, Arai H. Decrease in membrane phospholipid unsaturation induces unfolded protein response. J Biol Chem. 2010;285(29):22027–35.
pubmed: 20489212
pmcid: 2903364
doi: 10.1074/jbc.M110.126870
Pineau L, Colas J, Dupont S, Beney L, Fleurat-Lessard P, Berjeaud JM, et al. Lipid-induced ER stress: synergistic effects of sterols and saturated fatty acids. Traffic. 2009;10(6):673–90.
pubmed: 19302420
doi: 10.1111/j.1600-0854.2009.00903.x
Swinnen JV, Brusselmans K, Verhoeven G. Increased lipogenesis in cancer cells: new players, novel targets. Curr Opin Clin Nutr Metab Care. 2006;9(4):358–65.
pubmed: 16778563
doi: 10.1097/01.mco.0000232894.28674.30
Montesdeoca N, López M, Ariza X, Herrero L, Makowski K. Inhibitors of lipogenic enzymes as a potential therapy against cancer. Faseb j. 2020;34(9):11355–81.
pubmed: 32761847
doi: 10.1096/fj.202000705R
Volmer R, van der Ploeg K, Ron D. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc Natl Acad Sci. 2013;110(12):4628–33.
pubmed: 23487760
pmcid: 3606975
doi: 10.1073/pnas.1217611110
Garcia G, Zhang H, Moreno S, Tsui CK, Webster BM, Higuchi-Sanabria R, et al. Lipid homeostasis is essential for a maximal ER stress response. eLife. 2023;12:e83884.
pubmed: 37489956
pmcid: 10368420
doi: 10.7554/eLife.83884
Han J, Kaufman RJ. The role of ER stress in lipid metabolism and lipotoxicity. J Lipid Res. 2016;57(8):1329–38.
pubmed: 27146479
pmcid: 4959874
doi: 10.1194/jlr.R067595
Pinkham K, Park DJ, Hashemiaghdam A, Kirov AB, Adam I, Rosiak K, et al. Stearoyl CoA desaturase is essential for regulation of endoplasmic Reticulum Homeostasis and Tumor Growth in Glioblastoma Cancer Stem cells. Stem Cell Rep. 2019;12(4):712–27.
doi: 10.1016/j.stemcr.2019.02.012
Aljohani A, Khan MI, Syed DN, Abram B, Lewis S, Neill LO, et al. Hepatic Stearoyl-CoA desaturase-1 deficiency-mediated activation of mTORC1- PGC-1α axis regulates ER stress during high-carbohydrate feeding. Sci Rep. 2019;9(1):15761.
pubmed: 31673045
pmcid: 6823547
doi: 10.1038/s41598-019-52339-7
Minville-Walz M, Pierre A-S, Pichon L, Bellenger S, Fèvre C, Bellenger J, et al. Inhibition of Stearoyl-CoA desaturase 1 expression induces CHOP-Dependent cell death in Human Cancer cells. PLoS ONE. 2010;5(12):e14363.
pubmed: 21179554
pmcid: 3002938
doi: 10.1371/journal.pone.0014363
Song MJ, Malhi H. The unfolded protein response and hepatic lipid metabolism in non alcoholic fatty liver disease. Pharmacol Ther. 2019;203:107401.
pubmed: 31419516
pmcid: 6848795
doi: 10.1016/j.pharmthera.2019.107401
Celik C, Lee SYT, Yap WS, Thibault G. Endoplasmic reticulum stress and lipids in health and diseases. Prog Lipid Res. 2023;89:101198.
pubmed: 36379317
doi: 10.1016/j.plipres.2022.101198
Singh R. Autophagy and regulation of lipid metabolism. Results Probl Cell Differ. 2010;52:35–46.
pubmed: 20865370
pmcid: 4052896
doi: 10.1007/978-3-642-14426-4_4
Dall’Armi C, Devereaux KA, Di Paolo G. The role of lipids in the control of autophagy. Curr Biol. 2013;23(1):R33–45.
pubmed: 23305670
pmcid: 3587843
doi: 10.1016/j.cub.2012.10.041
Liu G, Feng S, Jia L, Wang C, Fu Y, Luo Y. Lung fibroblasts promote metastatic colonization through upregulation of stearoyl-CoA desaturase 1 in tumor cells. Oncogene. 2018;37(11):1519–33.
pubmed: 29326439
doi: 10.1038/s41388-017-0062-6
Li J, Condello S, Thomes-Pepin J, Ma X, Xia Y, Hurley TD, et al. Lipid desaturation is a metabolic marker and therapeutic target of ovarian Cancer stem cells. Cell Stem Cell. 2017;20(3):303–e145.
pubmed: 28041894
doi: 10.1016/j.stem.2016.11.004
Zhao G, Tan Y, Cardenas H, Vayngart D, Wang Y, Huang H, et al. Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids. Proc Natl Acad Sci U S A. 2022;119(41):e2203480119.
pubmed: 36197994
pmcid: 9564215
doi: 10.1073/pnas.2203480119
Xin Z, Zhao H, Serby MD, Liu B, Liu M, Szczepankiewicz BG, et al. Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors. Bioorg Med Chem Lett. 2008;18(15):4298–302.
pubmed: 18632269
doi: 10.1016/j.bmcl.2008.06.088
von Roemeling CA, Marlow LA, Pinkerton AB, Crist A, Miller J, Tun HW, et al. Aberrant lipid metabolism in anaplastic thyroid carcinoma reveals stearoyl CoA desaturase 1 as a novel therapeutic target. J Clin Endocrinol Metab. 2015;100(5):E697–709.
doi: 10.1210/jc.2014-2764
von Roemeling CA, Marlow LA, Wei JJ, Cooper SJ, Caulfield TR, Wu K, et al. Stearoyl-CoA desaturase 1 is a novel molecular therapeutic target for clear cell renal cell carcinoma. Clin Cancer Res. 2013;19(9):2368–80.
doi: 10.1158/1078-0432.CCR-12-3249
Piao C, Cui X, Zhan B, Li J, Li Z, Li Z, et al. Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer. J Cell Mol Med. 2019;23(3):2064–76.
pubmed: 30592142
doi: 10.1111/jcmm.14114
Angelucci C, D’Alessio A, Iacopino F, Proietti G, Di Leone A, Masetti R, et al. Pivotal role of human stearoyl-CoA desaturases (SCD1 and 5) in breast cancer progression: oleic acid-based effect of SCD1 on cell migration and a novel pro-cell survival role for SCD5. Oncotarget. 2018;9(36):24364–80.
pubmed: 29849946
pmcid: 5966257
doi: 10.18632/oncotarget.25273
Tracz-Gaszewska Z, Dobrzyn P. Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of Cancer. Cancers (Basel). 2019;11(7).
Bansal S, Berk M, Alkhouri N, Partrick DA, Fung JJ, Feldstein A. Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma. J Surg Res. 2014;186(1):29–38.
pubmed: 24135379
doi: 10.1016/j.jss.2013.07.001
Fritz V, Benfodda Z, Rodier G, Henriquet C, Iborra F, Avancès C, et al. Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice. Mol Cancer Ther. 2010;9(6):1740–54.
pubmed: 20530718
pmcid: 3315476
doi: 10.1158/1535-7163.MCT-09-1064
Noto A, De Vitis C, Pisanu ME, Roscilli G, Ricci G, Catizone A, et al. Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ. Oncogene. 2017;36(32):4671–2.
pubmed: 28628115
doi: 10.1038/onc.2017.212
Sen U, Coleman C, Sen T. Stearoyl coenzyme a desaturase-1: multitasker in cancer, metabolism, and ferroptosis. Trends Cancer. 2023;9(6):480–9.
pubmed: 37029018
doi: 10.1016/j.trecan.2023.03.003
Ascenzi F, De Vitis C, Maugeri-Saccà M, Napoli C, Ciliberto G, Mancini R. SCD1, autophagy and cancer: implications for therapy. J Experimental Clin Cancer Res. 2021;40(1):265.
doi: 10.1186/s13046-021-02067-6
Peláez R, Pariente A, Pérez-Sala Á, Larráyoz IM. Sterculic Acid: the mechanisms of Action beyond Stearoyl-CoA desaturase inhibition and Therapeutic opportunities in Human diseases. Cells. 2020;9(1):140.
pubmed: 31936134
pmcid: 7016617
doi: 10.3390/cells9010140
Brown JM, Rudel LL. Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: considerations for future drug discovery. Curr Opin Lipidol. 2010;21(3):192–7.
pubmed: 20216310
pmcid: 3099527
doi: 10.1097/MOL.0b013e32833854ac
Brigandi RA, Zhu J, Murnane AA, Reedy BA, Shakib S. A phase 1 Randomized, Placebo-Controlled Trial with a topical inhibitor of stearoyl-coenzyme A desaturase 1 under occluded and nonoccluded conditions. Clin Pharmacol Drug Dev. 2019;8(3):270–80.
pubmed: 30650256
pmcid: 6590436
doi: 10.1002/cpdd.644