Lipid composition of the cancer cell membrane

Journal of Bioenergetics and Biomembranes, Journal Year: 2020, Volume and Issue: 52(5), P. 321 - 342

Published: July 26, 2020

Abstract Cancer cell possesses numerous adaptations to resist the immune system response and chemotherapy. One of most significant properties neoplastic cells is altered lipid metabolism, consequently, abnormal membrane composition. Like in case phosphatidylcholine, these changes result modulation certain enzymes accumulation energetic material, which could be used for a higher proliferation rate. The are so prominent, that some lipids, such as phosphatidylserines, even considered cancer biomarkers. Additionally, biophysical membranes lead resistance chemotherapy, finally disturbances signalling pathways. Namely, increased levels like instance phosphatidylserine, attenuation response. Also, saturation prevent from demanding conditions microenvironment. Particularly interesting significance cholesterol content metastasis. This review paper discusses roles each type physiology. combined theoretical data with clinical studies show novel therapeutic options concerning oncology.

Language: Английский

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Cholesterol metabolism: New functions and therapeutic approaches in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2020, Volume and Issue: 1874(1), P. 188394 - 188394

Published: July 19, 2020

Language: Английский

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Obesity, Diabetes, and Increased Cancer Progression

Diabetes & Metabolism Journal, Journal Year: 2021, Volume and Issue: 45(6), P. 799 - 812

Published: Nov. 23, 2021

Rates of obesity and diabetes have increased significantly over the past decades prevalence is expected to continue rise further in coming years. Many observations suggest that are associated with an risk developing several types cancers, including liver, pancreatic, endometrial, colorectal, post-menopausal breast cancer. The path towards affected by multiple factors, adipokines, inflammatory cytokines, growth hormones, insulin resistance, hyperlipidemia. metabolic abnormalities changes levels these factors potential contribute development progression cancer through regulation distinct signaling pathways. Here, we highlight cellular molecular pathways constitute links between obesity, diabetes, mortality. This includes a description existing evidence supporting obesity-driven morphological functional alternations cells adipocytes complex interactions within tumor microenvironment.

Language: Английский

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Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Jan. 5, 2022

Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on growth of breast cancer cells; however, underlying molecular mechanisms for this are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as crucial driver progression. Adiponectin demonstrates wide range activities modulation lipid metabolism under physiological conditions. However, biological actions adiponectin in cancer-specific and its role regulation cell remain elusive.The effects fatty were evaluated by measuring cellular neutral pool, free level, oxidation (FAO). Colocalization between fluorescent-labeled droplets LC3/lysosomes was employed to detect lipophagy activation. Cell viability apoptosis examined MTS assay, caspase-3/7 activity measurement, TUNEL Annexin V binding assay. Gene expression determined real time-quantitative polymerase chain reaction (RT-qPCR) western blot analysis. The transcriptional SREBP-1 specific dsDNA modulatory roles SIRT-1 adiponectin-activated mediators confirmed gene silencing and/or using their pharmacological inhibitors. Observations vitro assays further validated an MDA-MB-231 orthotopic tumor model.Globular (gAcrp) prominently decreased pool different cells. deficiency promoted causing disruption rafts blocking raft-associated signal transduction. Mechanistically, dysregulated homeostasis induced two concerted actions: 1) suppression synthesis (FAS) through downregulation FAS-related enzymes, 2) stimulation lipophagy-mediated lipolysis FAO. Notably, induction critically contributed adiponectin-induced alterations. Finally, remodeling key nude mice bearing xenografts.This study elucidates multifaceted provides evidence connection cancer.

Language: Английский

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Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience

Cancer Letters, Journal Year: 2023, Volume and Issue: 559, P. 216119 - 216119

Published: March 7, 2023

Language: Английский

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Lipids as mediators of cancer progression and metastasis

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(1), P. 16 - 29

Published: Jan. 25, 2024

Language: Английский

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Accumulated cholesterol protects tumours from elevated lipid peroxidation in the microenvironment

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102678 - 102678

Published: March 15, 2023

Elevated lipid peroxidation (LPO), usually present in the tumour microenvironment (TME), is profoundly implicated antitumour immunity and may be targeted for development of new therapies. However, cells also rewire their metabolism to survive elevated LPO. Here, we report a novel nonantioxidant mechanism by which benefit from accumulated cholesterol restrain LPO ferroptosis, nonapoptotic form cell death characterized Modulating metabolism, especially LDLR-mediated uptake, shifted susceptibility ferroptosis. Elevation cellular content specifically restrained triggered GSH-GPX4 inhibition or oxidizing factors TME. Furthermore, depletion TME MβCD efficiently enhanced efficacy ferroptosis mouse xenograft model. Distinct antioxidant effect its metabolic intermediates, protective role was ascribed ability decrease membrane fluidity promote raft formation, affects diffusion substrates. A correlation between rafts found tissues renal cancer patients. Together, our findings have identified general nonsacrificial suppresses LPO, can exploited enhance ferroptosis-based strategies.

Language: Английский

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Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications

Molecules, Journal Year: 2023, Volume and Issue: 28(13), P. 5246 - 5246

Published: July 6, 2023

Cellular signaling pathways involved in the maintenance of equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited prevention treatment cancer. Epigallocatechin-3-gallate (EGCG) is most abundant phenolic compound found green tea. It has been shown to regulate multiple crucial cellular pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, others. Deregulation abovementioned pathophysiology demonstrated EGCG may exert anti-proliferative, anti-inflammatory, apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical clinical studies suggest used numerous disorders, This review aims summarize existing knowledge regarding biological properties EGCG, especially context cancer prophylaxis.

Language: Английский

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Lipid Rafts in Signalling, Diseases, and Infections: What Can Be Learned from Fluorescence Techniques?

Membranes, Journal Year: 2025, Volume and Issue: 15(1), P. 6 - 6

Published: Jan. 1, 2025

Lipid rafts are dynamic microdomains in the membrane, rich cholesterol and sphingolipids, that critical for biological processes like cell signalling, membrane trafficking, protein organization. Their essential role is claimed both physiological pathological conditions, including cancer, neurodegenerative diseases, viral infections, making them a key area of research. Fluorescence-based approaches, super-resolution fluorescence microscopy techniques, enable precise analysis organization, dynamics, interactions these microdomains, thanks also to innovative design appropriate fluorescent probes. Moreover, non-invasive approaches allow study live cells, facilitating collection quantitative data under physiologically relevant conditions. This review synthesizes latest insights into lipid underscores how techniques have advanced our understanding microdomains. The findings emphasize pivotal health disease, providing foundation future research potential therapeutic interventions.

Language: Английский

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Lipid rafts as a therapeutic target

Journal of Lipid Research, Journal Year: 2020, Volume and Issue: 61(5), P. 687 - 695

Published: March 23, 2020

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing pathway components in ordered microdomains on cell surface. Cellular responses regulated lipid range from physiological to pathological, success a therapeutic approach targeting “pathological” depends ability remedial agent recognize them disrupt pathological without affecting normal raft-dependent functions. In this article, concluding Thematic Review Series Biology Rafts, we review current experimental therapies rafts, including examples inflammarafts clusters apoptotic molecule-enriched rafts. The corrective approaches include regulation cholesterol sphingolipid metabolism membrane trafficking using HDL its mimetics, LXR agonists, ABCA1 overexpression, cyclodextrins, as well more targeted intervention with apoA-I binding protein. Among others, highlight design antagonists that target inflammatory receptors only their activated form homo- or heterodimers, when receptor dimerization occurs Other aim promote functions, such augmenting caveolae-dependent tissue repair. overview highly dynamic field will provide readers view emerging concept strategy. protein β-cyclodextrin cluster caveolin-1 chemotherapy-induced peripheral neuropathy human immunodeficiency virus methyl-β-cyclodextrin µ-opioid Niemann-Pick type C play unique role physiology providing solid platform within where macromolecular complexes can assemble battling forces chaos disorderly liquid phase surroundings. abundance functional properties change rapidly response changing conditions, most likely representing fundamentally important layer fast regulation, connecting coordinating broad pathways. At same time, described articles published series, dysregulation plays key pathogenesis hematopoietic, neurological, inflammatory, infectious diseases, cancer. roles point an exciting possibility for purposes. Targeting early step has significant advantage addressing “a root” problem mitigating diverse consequences raft pathology. For example, neurodegenerative diseases may simultaneously reduce amyloidogenic misfolding processing neuroinflammation, two elements neurodegeneration. mitigate infection comorbidities. Given inflammation multitude processes, moderate have utility. However, is not problems. Primum non nocere, “first, do no harm.” question inevitably comes mind, it really possible essential component plasma organization physiologic achieve effect adverse impact? Two observations indicate might be realistic possibility. First, somewhat surprisingly, raft-associated pathologies are caused “excessive” rafts: elevated increased stability, both. Further, β-cyclodextrins (βCDs) effective tool deplete cells indiscriminately destroy Although at high concentrations they cytotoxic, used lower still but remarkably few effects vitro vivo. This points existence redundancy and/or backup mechanisms supporting Second spatial temporal heterogeneity relation size, structure, and, ultimately, function. Raft determined repertoire lipids proteins opens, least theoretically, selectively one subset other, function type, all them. goal article demonstrate recent advances understanding excessive viable There major remodeling One mechanism relies availability critical principally, sphingolipids. Depletion methyl-βCD (MβCD) classical method break down significantly attenuating originating Inhibition biosynthesis also lowers content alters raft-originated (1Zhuang L. Kim J. Adam R.M. Solomon K.R. Freeman M.R. Cholesterol composition survival prostate cancer xenografts.J. Clin. Invest. 2005; 115: 959-968Crossref PubMed Scopus (438) Google Scholar). 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Fatty modulate 4 through recruitment into reactive oxygen species-dependent manner.J. 284: 27384-27392Abstract (406) 12Zhu Owen Wilson M.D. H. Griffiths G.L. Thomas Hiltbold E.M. Fessler Macrophage reduces MyD88-dependent Toll-like reduction cholesterol.J. 2010; 51: 3196-3206Abstract (246) 13Shridas P. Bailey W.M. Talbott Oslund R.C. Gelb M.H. Webb N.R. Group X secretory phospholipase A2 enhances macrophages.J. 482-489Crossref (25) 14Woller S.A. S.H. E.J. Low Schneider Ramachandran Bae Y.S. Sviridov Corr al.Inhibition AIBP: spinal facilitated states.Cell Rep. 23: 2667-2677Abstract (34) Scholar) IFNγ (15Sehgal P.B. Guo G.G. Shah Kumar V. Cytokine signaling: STATS rafts.J. 277: 12067-12074Abstract (153) 16Kim J.H. D.J. Jeong H.K. D.W. S.Y. Park S.M. Suh Y.H. Jou I. Joe E.H. DJ-1 facilitates interaction between STAT1 phosphatase, SHP-1, brain microglia astrocytes: novel anti-inflammatory DJ-1.Neurobiol. Dis. 2013; 60: 1-10Crossref (66) association TREM2 molecule DAP12 (17Poliani P.L. Fontana Robinette M.L. Yamanishi Gilfillan Colonna sustains microglial expansion during aging demyelination.J. 2015; 125: 2161-2170Crossref (289) NADPH oxidase complex (18Vilhardt F. van Deurs B. phagocyte cholesterol-enriched assembly.EMBO 739-748Crossref (150) among lead clustering larger stable units, sphingolipids disrupts inflammarafts. efflux agonists cells, (AIBP) (the treatment highlighted separate section below), could strategy cells. CASMER designates supramolecular hub playing central death receptor-mediated apoptosis localizing (19Gajate Mollinedo Cytoskeleton-mediated concentration forms apoptosis-promoting chemotherapy.J. 280: 11641-11647Abstract (159) 20Gajate Gonzalez-Camacho connection extrinsic intrinsic pathways.Biochem. Commun. 380: 780-784Crossref (84) aggregated forming CASMERs complexity recruited proteins, Fas/CD95 TNFR1 (CD120a) 21Lotocki G. Alonso O.F. Dietrich W.D. Keane R.W. Tumor necrosis factor 1 intermediates traumatized brain.J. Neurosci. 24: 11010-11016Crossref (62) TRAIL TRAIL-R1 (DR4) TRAIL-R2 (DR5) 22Marconi Ascione Ciarlo Vona Garofalo Sorice Gianni A.M. Locatelli S.L. Carlo-Stella Malorni al.Constitutive localization DR4 mandatory TRAIL-induced B-cell hematologic malignancies.Cell Death 4: e863Crossref (33) downstream molecules, FADD, procaspase-8, procaspase-10, death-inducing (20Gajate 23Gajate Edelfosine perifosine selective multiple myeloma rafts.Blood. 2007; 109: 711-719Crossref (241) 24Gajate Involvement aggregates enriched antileukemic action edelfosine Jurkat cells.PLoS One. e5044Crossref (91) It remarkable regulatory redistributed non-raft (25Mollinedo, F., C., Gajate, hubs survival/death invasion: tumor progression therapy. January 27, 2020; doi:10.1194/jlr.TR119000439.Google Compared contain higher levels cholesterol, facilitating cholesterol-rich CASMERs. pivot makes another distinctive potential here would than CASMERs, below. AIBP (gene name APOA1BP, known NAXE) discovered yeast two-hybrid screen bind (26Ritter Buechler Boettcher A. Barlage Schmitz-Madry Orso Bared Schmiedeknecht Baehr C.H. Fricker al.Cloning apolipoprotein A-I protein, AI-BP, secreted kidney proximal tubules ApoA-I.Genomics. 79: 693-702Crossref (63) shown endothelial macrophages, (14Woller 27Fang Baek Liu Almazan Ulrich Wiesner Taleb Deer Pattison al.Control angiogenesis AIBP-mediated efflux.Nature. 498: 118-122Crossref (134) 28Zhang Xie Wu J.F. Yao Tan Y.L. Xia X.D. X.Y. Lan al.Apolipoprotein A-1 promotes macrophage preventing degradation.Atherosclerosis. 2016; 248: 149-159Abstract (56) 29Choi Wallace Burg Alekseeva Ubags N.D. Cool C.D. Fang Suratt B.T. al.AIBP augments alveolar macrophages surfactant acute lung inflammation.JCI Insight. 3: 120519Crossref (24) binds Surface TLR4, localized inflammarafts, stimulated LPS until internalized endocytosis (30Zanoni Ostuni Marek L.R. Barresi Barbalat Barton G.M. Granucci Kagan J.C. CD14 controls LPS-induced 4.Cell. 147: 868-880Abstract (618) increases recombinant leads enhanced reduced affords selectivity mode action: little nonactivated reversing back observed single intrathecal dose reverses tactile allodynia (pain light touch) mouse models (CIPN) arthritis, lasting long over 2 months CIPN model. accompanied motor sensory mice Inhaled injury (29Choi AAV-mediated sustained hyperlipidemia atherosclerosis Ldlr−/− fed Western diet (31Schneider Agatisa-Boyle Zhu Sears D.D. Gordts Miller Y.I. protects against abnormalities atherosclerosis.J. 59: 854-863Abstract (29) 32Zhang Zhao G.J. Gong Z.W. Chen L.Y. Zheng X.L. Tang X.E. C.K. promoting reverse transport ameliorating apoE(-/-) mice.Atherosclerosis. 273: 122-130Abstract (31) (HIV) replication humanized (33Dubrovsky Ward S-H. Pushkarsky Brichacek Vanpouille Adzhubei A.A. Mukhamedova Margolis HIV rafts.MBio. 11: e02956-19Crossref (22) data evidence TLR4-mediated mediate well, depending pathologic By virtue abundance, addition inhibits enzymes, channels hypothesis needs validation. transcriptional regulator (among genes), presence agonist, stimulates these transporters. both actin polymerization mechanisms. “lipid” efflux. amount potentiating vice versa (34Lai Azzam K.M. Lin W-C. Rai Lowe J.M. Gabor K.A. Madenspacher Aloor Näär al.MicroRNA-33 innate immune ATP cassette transporter-mediated microdomains.J. 291: 19651-19660Abstract (43) probably responsible ABCG1- ABCA1/ABCG1-deficient “cytoskeleton” activate small GTPase Cdc42, (35Nofer J-R. Remaley Feuerborn Wolinnska Engel von Eckardstein Assmann Apolipoprotein activates Cdc42 transporter.J. 2006; 47: 794-803Abstract (60) 36Nofer Levkau Sokoll Seedorf U. Signaling ApoA-I-induced Efflux.J. 2003; 278: 53055-53062Abstract (59) 37Kheirollah Nagayasu Ueda Yokoyama Michikawa Ito cdc42/Rho kinase ApoA-I-mediated cytosolic lipid-protein particles microtubules rat astrocytes.J. 92: 455-463Crossref (11) subsequent negative reciprocal: determines (38Landry Y.D. Denis Nandi Bell Vaughan Zha ATP-binding transporter A1 ATPase-related functions.J. 281: 36091-36101Abstract (184) Scholar); activity stability (39Klappe Hummel Hoekstra Kok J.W. dependence function.Chem. Phys. Lipids. 161: 57-64Crossref (95) been vivo (40Noghero Perino Seano Saglio Sasso Veglio Primo Hirsch Bussolino Morello Liver impairing vascular growth receptor-2.Arterioscler. Thromb. Vasc. 2012; 32: 2280-2288Crossref (58) 41Sun T-W. Expression liver genes decreases amyloid {beta} peptide secretion.J. 27688-27694Abstract (165) 42Ramezani Dubrovsky Karandish Raj D.S. Fitzgerald Bukrinsky Stimulation potent anti-HIV infection.J. Pharmacol. Exp. Ther. 354: 376-383Crossref (13) many involved pathways, contribution overall outcome difficult ascertain.

Language: Английский

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