Targeting Ferroptosis to Iron Out Cancer

Cancer Cell, Journal Year: 2019, Volume and Issue: 35(6), P. 830 - 849

Published: May 16, 2019

Language: Английский

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Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer

Cell Metabolism, Journal Year: 2019, Volume and Issue: 31(1), P. 62 - 76

Published: Dec. 5, 2019

Language: Английский

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Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1056 - 1056

Published: April 29, 2021

Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These alterations include (1) a shift from oxidative phosphorylation aerobic glycolysis support the increased need for ATP, (2) glutaminolysis NADPH regeneration, (3) altered flux through pentose phosphate pathway tricarboxylic acid cycle macromolecule generation, (4) lipid uptake, lipogenesis, cholesterol synthesis, (5) upregulation of one-carbon metabolism production NADH/NADPH, nucleotides, glutathione, (6) amino metabolism, (7) metabolism-based regulation apoptosis, (8) utilization alternative substrates, such as lactate acetate. Altered in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, other regulatory molecules, including non-coding RNAs. Changes pathways are dynamic, exhibit plasticity, often dependent on type microenvironment, leading thought Warburg Effect "reverse Effect" plasticity. Understanding complex nature these multiple can development new therapies.

Language: Английский

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Metabolism of Amino Acids in Cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 8

Published: Jan. 12, 2021

Metabolic reprogramming has been widely recognized as a hallmark of malignancy. The uptake and metabolism amino acids are aberrantly upregulated in many cancers that display addiction to particular acids. Amino facilitate the survival proliferation cancer cells under genotoxic, oxidative, nutritional stress. Thus, targeting acid is becoming potential therapeutic strategy for patients. In this review, we will systematically summarize recent progress malignancy discuss their interconnection with mammalian target rapamycin complex 1 (mTORC1) signaling, epigenetic modification, tumor growth immunity, ferroptosis. Finally, highlight applications.

Language: Английский

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Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(2), P. 229 - 242.e8

Published: June 18, 2020

Language: Английский

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Lipid metabolism in cancer progression and therapeutic strategies

MedComm, Journal Year: 2020, Volume and Issue: 2(1), P. 27 - 59

Published: Dec. 24, 2020

Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, source material for biogenesis of cell membranes. The enhanced synthesis, storage, uptake contribute to cancer progression. rewiring has been linked activation oncogenic pathways cross talk with tumor microenvironment. resulting activity favors survival proliferation cells harsh conditions within tumor. Lipid also plays a vital role immunogenicity via effects on function noncancer microenvironment, especially immune-associated cells. Targeting altered shown potential promising anticancer therapy. Here, we review recent evidence implicating contribution reprogramming progression, discuss molecular mechanisms underlying cancer, therapeutic strategies directed toward This sheds new light fully understanding context provides valuable clues targeting

Language: Английский

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Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy

Journal of Lipid Research, Journal Year: 2020, Volume and Issue: 61(5), P. 611 - 635

Published: Jan. 27, 2020

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation proteins may modulate accessibility to regulatory effector molecules. Thus, serve sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels intracellular cholesterol than their normal non-tumorigenic counterparts. Many processes involved cancer development (insulin-like growth factor system phosphatidylinositol 3-kinase-AKT) metastasis [cluster differentiation (CD)44] are dependent on modulated by rafts. Additional playing an important several malignant cancers (e.g., transmembrane glycoprotein mucin 1) also being detected association with suggesting major tumor progression. Conversely, scaffolds recruitment clustering Fas/CD95 death receptors downstream molecules leading cell death-promoting raft platforms. The partition aggregated has led formation so-called cluster apoptotic molecule-enriched CASMER, which leads apoptosis amplification can be pharmacologically modulated. These viewed linchpin from signals launched. In this review, we discuss involvement cells, including survival, death, metastasis, consider potential modulation promising target therapy. disintegrin metalloproteinase 10 domain death-inducing complex receptor 4 5 extracellular matrix epidermal estrogen Fas-associated protein glycosylphosphatidylinositol hyaluronic acid heat shock 90 insulin-like type 1 insulin substrate c-Jun N-terminal kinase mantle lymphoma mammalian rapamycin phosphatidylinositol-dependent pleckstrin homology 3-kinase 3,4,5-trisphosphate phosphatase tensin homolog TNF superfamily TNF-related apoptosis-inducing ligand Lipids components essential maintenance integrity numerous biological functions, division, they act energy sources tissues. Altered metabolism is newly recognized feature malignancy. For example, increased uptake, storage, occur variety contribute (1Swinnen J.V. Brusselmans K. Verhoeven G. Increased lipogenesis cells: new players, novel targets.Curr. Opin. Clin. Nutr. Metab. Care. 2006; 9: 358-365Crossref PubMed Scopus (422) Google Scholar, 2Cheng C. Geng F. Cheng X. Guo D. Lipid reprogramming its targets cancer.Cancer Commun. (Lond.). 2018; 38: 27Crossref (90) Scholar). Cholesterol component membranes, comprising about 30% bilayer, it plays crucial function viability. building block plasma (Fig. 1), pivotal roles maintaining structural regulating permeability fluidity membranes well initiation adhesion (ECM) (3Chapman Phase transitions characteristics lipids membranes.Q. Rev. Biophys. 1975; 8: 185-235Crossref 4Jaipuria Ukmar-Godec T. Zweckstetter M. Challenges approaches understand cholesterol-binding impact function: NMR view.Cell. Mol. Life Sci. 75: 2137-2151Crossref (13) addition central biogenesis cellular organization, serves precursor different that physiology cancer, steroid hormones, oxysterols, vitamin D, estrogen-related α (5Chimento A. Casaburi I. Avena P. Trotta De Luca Rago V. Pezzi Sirianni R. metabolites growth: therapeutic statins treatment.Front. Endocrinol. (Lausanne). 2019; 807Crossref (12) Scholar), even opposite actions progression 1). 27-hydroxycholesterol, most abundant oxysterol plasma, oxygenated derivatives formed enzymatic radical oxidation, affect distinct tumors way (6Kloudova Guengerich F.P. Soucek oxysterols human cancer.Trends 2017; 28: 485-496Abstract Full Text PDF (65) Oxysterols have been reported promote proliferation (7Wu Q. Ishikawa Tang H. McDonald J.G. Yuhanna I.S. Thompson B. Girard L. Mineo Brekken R.A. et al.27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast growth.Cell Reports. 2013; 5: 637-645Abstract (0) recruit pro-tumor neutrophils (8Raccosta Fontana Maggioni Lanterna Villablanca E.J. Paniccia Musumeci Chiricozzi E. Trincavelli M.L. Daniele S. al.The oxysterol-CXCR2 axis key tumor-promoting neutrophils.J. Exp. Med. 210: 1711-1728Crossref (102) 9Soncini Corna Moresco Coltella N. Restuccia U. Raccosta Lin C.Y. Invernizzi Crocchiolo al.24-Hydroxycholesterol participates pancreatic neuroendocrine development.Proc. Natl. Acad. USA. 2016; 113: E6219-E6227Crossref seem (10Mollinedo Neutrophil degranulation, plasticity, metastasis.Trends Immunol. 40: 228-242Abstract (52) facilitate 11Baek A.E. Yu Y.A. He Wardell S.E. Chang Kwon Pillai R.V. McDowell H.B. J.W. Dubois L.G. metabolite 27 hydroxycholesterol facilitates through immune cells.Nat. 864Crossref (107) However, suppress acting ligands LXRs (12Vedin L.L. Lewandowski S.A. Parini Gustafsson J.A. Steffensen K.R. LXR inhibits cells.Carcinogenesis. 2009; 30: 575-579Crossref (125) 13Vedin LXRalpha LXRbeta colon.Mol. Carcinog. 52: 835-844Crossref Another steroid, shown exert chemoprotective action tumors, such colorectal prostate (14Theodoratou Farrington S.M. Tenesa McNeill Cetnarskyj Barnetson Porteous M.E. Dunlop M.G. Campbell Modification inverse between dietary D intake risk FokI variant supports Vitamin mediated VDR binding.Int. J. Cancer. 2008; 123: 2170-2179Crossref (47) 15Li Stampfer M.J. Hollis J.B. Mucci L.A. Gaziano J.M. Hunter Giovannucci E.L. Ma A prospective study metabolites, polymorphisms, cancer.PLoS 2007; 4: e103Crossref (226) number other functions. It estrogens, high associated (16Yager J.D. Davidson N.E. Estrogen carcinogenesis cancer.N. Engl. 354: 270-282Crossref (1259) As stated above, functional endogenous agonist α, fatty metabolism, skeletal homeostasis mitochondrial (17Wei W. Schwaid A.G. Wang Chen Chu Saghatelian Wan Y. Ligand activation ERRalpha mediates statin bisphosphonate effects.Cell 23: 479-491Abstract 18Casaburi Chimento Nocito Sculco agonist: perspective 525Crossref (7) above processes, regulator responsible close packing acyl chains phospholipids, promoting phase separation, stabilizing cholesterol- sphingolipid-rich microdomains (19Simons Ikonen Functional membranes.Nature. 1997; 387: 569-572Crossref (7622) 20Maxfield F.R. van Meer Cholesterol, cells.Curr. Cell Biol. 2010; 22: 422-429Crossref (191) constitute centers organization trafficking (21Simons Toomre transduction.Nat. 2000; 1: 31-39Crossref 22Ikonen Roles transport.Curr. 2001; 13: 470-477Crossref (531) 23Mollinedo Gajate regulation cancer.Adv. Regul. 2015; 57: 130-146Crossref (162) On hand, androgens, (24Pelton Freeman M.R. Solomon cancer.Curr. Pharmacol. 2012; 12: 751-759Crossref (138) preclinical studies mouse models showed enhanced mice fed cholesterol-enriched diet (25Llaverias Danilo Witkiewicz A.K. Daumer Lisanti M.P. Frank P.G. Western-type accelerates autochthonous model cancer.Am. Pathol. 177: 3180-3191Abstract (73) varying ways, generation required proliferating wide array diverse pro- anti-tumor functions Importantly, fate. either obtained synthesized de novo cell. content narrowly balanced metabolic intrinsic distribution organism, homeostatic mechanism seems disrupted cells. early 1900s, reports (26Jowett phosphatide contents tissues.Biochem. 1931; 25: 1991-1998Crossref 27Yasuda Bloor W.R. tumors.J. Invest. 1932; 11: 677-682Crossref 28Roffo A.H. Heliotropism relation skin 1933; 17: 42-57Crossref 29Knudson Sturges Bryan skin, blood, tissue rats irradiated ultraviolet light.J. Chem. 1939; 128: 721-727Abstract 30Mulas M.F. Abete Pulisci Pani Massidda Dessi Mandas esters regulators lymphocytic leukaemia cells.Cell Prolif. 2011; 44: 360-371Crossref Scholar) were surrounding tissues compared derived. now generally accepted tend types (31Krycer J.R. 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Sondhi links hypercholesterolemia pathophysiology.Science. 342: 1094-1098Crossref (423) 38Radišauskas Kuzmickiene Milinaviciene Everatt Hypertension, risk: review epidemiological evidence.Medicina (Kaunas). 89-98Crossref 39Jamnagerwalla Howard L.E. Allott E.H. Vidal A.C. Moreira D.M. Castro-Santamaria Andriole G.L. Freedland S.J. high-grade results REDUCE study.Prostate Prostatic Dis. 21: 252-259Crossref (18) obesity types; hypercholesterolemia, obesity-associated comorbidity, inflammation (40Calle E.E. Kaaks Overweight, proposed mechanisms.Nat. 2004; 579-591Crossref 41Allott Masko E.M. Obesity weighing evidence.Eur. Urol. 63: 800-809Abstract (298) not clear. Different provided inconclusive contradictory results, positive elevated level certain no (33Kuzu low LDLs, transport receptor-mediated mechanisms, but genetically reduced LDL was not, thus per se do cause (42Benn Tybjaerg-Hansen Stender Frikke-Schmidt Nordestgaard B.G. Low-density lipoprotein mendelian randomization study.J. 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Hughes Murray L.J. after diagnosis survival: population-based Oncol. 32: 3177-3183Crossref 51Epstein M.M. Divine Chao Wells K.E. Feigelson H.S. Scholes Roblin Ulcickas Yood Engel L.S. Taylor al.Statin myeloma: analysis research network.Int. 141: 480-487Crossref (9) 52Van Rompay M.I. Nickel J.C. Ranganathan Kantoff P.W. McKinlay Prostate among using non-statin lipid-lowering medications.Eur. 112: 118-126Abstract 53Akinwunmi Vitonis A.F. Titus Terry K.L. Cramer D.W. therapy ovarian New England Case Control (NEC) study.Int. 144: 991-1000Crossref suggests could appearance cancer. contrast, did find (54Shepherd Blauw G.J. Murphy M.B. Bollen Buckley Cobbe Ford Gaw Hyland Jukema al.Pravastatin elderly individuals at vascular (PROSPER): randomised controlled trial.Lancet. 2002; 360: 1623-1630Abstract (2806) 55Beckwitt C.H. Brufsky Oltvai Z.N. reduce recurrence mortality.Breast 20: 144Crossref (42) Overall, mixed largely both question particular used (56Clendening Penn L.Z. Targeting statins.Oncogene. 31: 4967-4978Crossref (146) Statins inhibit rate-limiting enzyme converts HMG-CoA into mevalonate, turn synthesis products, cholesterol, ubiquinone, dolichol, isoprenoids geranylgeranyl pyrophosphate farnesyl bind small GTP-binding proteins, RAS RHO, facilitating translocation cytosol (57Gbelcová Lenicek Zelenka Knejzlik Dvorakova Zadinova Pouckova Kudla Balaz Ruml al.Differences antitumor effects various cancer.Int. 122: 1214-1221Crossref (81) 58Gbelcová Rimpelova Sachova Kolar Strnad Repiska D'Acunto W.C. Vitek Isoprenoids prenylation cells.Lipids Health 16: 250Crossref (8) inhibition mevalonate pathway provokes pleiotropic effects, although sensitivity lines varies, ambiguous clinical trials (59Göbel Breining Rauner Hofbauer L.C. Rachner T.D. Induction 3-hydroxy-3-methylglutaryl-CoA reductase resistance Death 10: 91Crossref (24) Unlike epidemiologic abnormal risk, compelling laboratory studies. latter indicate capable proliferation, migration, pathways mammary cancers. vivo indicated regulate (45Danilo Neoplastic diseases particularly (60Tosi Tugnoli Cholesteryl malignancy.Clin. Chim. 359: 27-45Crossref (72) Because follows rapidly require Alterations increase cholesteryl suggested to: biosynthesis HMG-CoA-reductase synthesis; 2) uptake exogenous overexpression LDL-receptor, LDLs bloodstream transporters cholesterol; 3) esterification acyltransferase ester storage droplets (61Petan Jarc Jusovic guardians fat stressful world.Molecules. E1941Crossref (78) Scholar); 4) lower efflux dynamic nature together uneven specialized where selectively included excluded. structurally heterogeneous discrete domains unique physical properties, coexistence liquid-disordered liquid-ordered phases same bilayer. 1997, Simons hypothesis, defined sphingolipids lipid-ordered platforms, move within fluid subdomains enriched glycosphingolipids phospholipids acylated saturated acids. assemblies harbor molecules, so float freely bilayer sizes depending composition, clustered form larger stabilized consensus definition emerged 2006 Keystone Symposium Rafts Function held Steamboat Springs, CO, follows: "membrane (10–200 nm), heterogeneous, highly dynamic, sterol- sphingolipid-enriched compartmentalize processes. Small sometimes protein-protein protein-lipid interactions" (Ref. 62Pike defined: report Function.J. 47: 1597-1598Abstract (963) Scholar; p. 1597). tight interactions sterols lead characteristic solubilization

Language: Английский

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Mechanisms for Modulating Anoikis Resistance in Cancer and the Relevance of Metabolic Reprogramming

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: March 29, 2021

The attachment of cells to the extracellular matrix (ECM) is hallmark structure–function stability and well-being. ECM detachment in localized tumors precedes abnormal dissemination tumor culminating metastasis. Programmed cell death (PCD) activated during tumorigenesis clear off ECM-detached through “anoikis.” However, cancer develop several mechanisms for abrogating anoikis, thus promoting their invasiveness Specific factors, such as growth proteins, pH, transcriptional signaling pathways, oxidative stress, have been reported drivers anoikis resistance, enhancing proliferation Recent studies highlighted key contributions metabolic enabling bypass anoikis. Therefore, understanding driving resistance could help counteract progression prevent This review elucidates dynamics employed by impede proliferation, invasion, In addition, authors discussed other intermediates (especially amino acids nucleotides) that are less explored, which be crucial

Language: Английский

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ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of glucose and lipid metabolism

European Journal of Medicinal Chemistry, Journal Year: 2018, Volume and Issue: 157, P. 1276 - 1291

Published: Sept. 1, 2018

Language: Английский

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Cancer as a Metabolic Disorder

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1155 - 1155

Published: Jan. 21, 2022

Cancer has long been considered a genetic disease characterized by myriad of mutations that drive cancer progression. Recent accumulating evidence indicates the dysregulated metabolism in cells is more than hallmark but may be underlying cause tumor. Most well-characterized oncogenes or tumor suppressor genes function to sustain altered metabolic state cancer. Here, we review supporting including key alterations glucose, glutamine, and fatty acid metabolism. Unlike do not occur all types, are common among subtypes across cancers. Recognizing as disorder could unravel diagnostic treatments markers can impact approaches used management.

Language: Английский

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