A New Target for the Treatment of Cancer: Lipid Droplets

Yıl 2026, Cilt: 11 Sayı: 1, 88 - 98, 15.03.2026

Seher Şahin , Özen Özensoy Güler , Ender Şimşek

https://doi.org/10.26453/otjhs.1674245

https://izlik.org/JA52YU88DZ

Öz

Cancer is characterized by the uncontrolled proliferation of cells and their ability to spread to distant tissues. Metabolic reprogramming is a hallmark of cancer, and dysregulation of lipid metabolism represents one of the most prominent metabolic alterations in tumor cells. In this context, lipid droplets (LDs) play a key role by supporting energy production and redox homeostasis, regulating autophagy, directing membrane synthesis, and modulating membrane composition. Through these functions, LDs help tumor cells minimize metabolic stress and facilitate tumor progression. LDs are dynamic organelles present in eukaryotic cells, consisting of a hydrophobic core of neutral lipids surrounded by a phospholipid monolayer. By regulating lipid storage and mobilization, LDs directly influence essential cellular processes required for survival, growth, and proliferation, including energy metabolism, membrane and organelle biogenesis, cell signaling, and gene transcription. This review addresses the composition and synthesis of LDs and examines their critical roles in cancer development, focusing particularly on selected cancer types.

Anahtar Kelimeler

Cancer , lipid droplet , lipid energy metabolism

Etik Beyan

This study is a review article; ethics committee approval is not required.

Kanser Tedavisinde Yeni Bir Hedef: Lipit Damlacıkları

https://izlik.org/JA52YU88DZ

Öz

Kanser, hücrelerin kontrolsüz çoğalması ve uzak dokulara yayılma yeteneği ile karakterize edilir. Metabolik yeniden programlama, kanserin ayırt edici özelliklerinden biridir ve lipit metabolizmasının düzensizliği, tümör hücrelerindeki en belirgin metabolik değişikliklerden birini temsil etmektedir. Bu bağlamda, lipit damlacıkları (LD'ler), enerji üretimini ve redoks homeostazını destekleyerek, otofajiyi düzenleyerek, membran sentezini yönlendirerek ve membran bileşimini modüle ederek önemli bir rol oynar. Bu işlevler aracılığıyla LD'ler, tümör hücrelerinin metabolik stresi en aza indirmesine ve tümör ilerlemesini kolaylaştırmasına yardımcı olur. LD'ler, ökaryotik hücrelerde bulunan, nötr lipitlerden oluşan hidrofobik bir çekirdek ve etrafını saran bir fosfolipid tek tabakasından oluşan dinamik organellerdir. Lipit depolama ve mobilizasyonunu düzenleyerek, LD'ler, enerji metabolizması, membran ve organel biyogenezi, hücre sinyalleşmesi ve gen transkripsiyonu dahil olmak üzere hayatta kalma, büyüme ve çoğalma için gerekli olan temel hücresel süreçleri doğrudan etkiler. Bu derlemede, LD'lerin bileşimi ve sentezi ele alınmakta ve özellikle seçilmiş kanser türlerine odaklanarak, kanser oluşumundaki kritik rolleri incelenmektedir.

Anahtar Kelimeler

Kanser , lipit damlacığı , lipit enerji metabolizması

Etik Beyan

Bu çalışma bir derleme makalesidir; etik kurul onayı gerekmemektedir.

Kaynakça

• 1. Ada S, Ertürk C, Uçar A, Akyüz S, Doğan F, Yücel B. Kanser Hücre Metabolizması. Türkiye Sağlık Enstitüleri Başkanlığı Dergisi. 2021; 66-75
• 2. National Cancer Institute (NCI). The Definition of Cancer. https://www.cancer.gov/about-cancer/understanding/what-is-cancer#definition. Accessed October 12, 2024
• 3. Senga SS, Grose RP. Hallmarks of cancer-the new testament. Open Biol. 2021;11(1):200358. doi:10.1098/rsob.200358
• 4. Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368(6487):eaaw5473. doi:10.1126/science.aaw5473
• 5. Hanahan D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022;12(1):31-46. doi:10.1158/2159-8290.CD-21-1059
• 6. Liu H, Zhang Z, Song L, Gao J, Liu Y. Lipid metabolism of cancer stem cells. Oncol Lett. 2022;23(4):119. doi:10.3892/ol.2022.13239
• 7. Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021;218(1):e20201606. doi:10.1084/jem.20201606
• 8. Schwartsburd P. Lipid droplets: could they be involved in cancer growth and cancer-microenvironment communications?. Cancer Commun (Lond). 2022;42(2):83-87. doi:10.1002/cac2.12257
• 9. Walther TC, Farese RV Jr. Lipid droplets and cellular lipid metabolism. Annu Rev Biochem. 2012;81:687-714. doi:10.1146/annurev-biochem-061009-102430
• 10. Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368(6487):eaaw5473. doi:10.1126/science.aaw5473
• 11. Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 2016;73(2):377-392. doi:10.1007/s00018-015-2070-4
• 12. Nong S, Han X, Xiang Y, et al. Metabolic reprogramming in cancer: Mechanisms and therapeutics. MedComm (2020). 2023;4(2):e218. doi:10.1002/mco2.218
• 13. Liu X, Zhang P, Xu J, Lv G, Li Y. Lipid metabolism in tumor microenvironment: novel therapeutic targets. Cancer Cell Int. 2022;22(1):224. doi:10.1186/s12935-022-02645-4
• 14. Schwartsburd P. Lipid droplets: could they be involved in cancer growth and cancer-microenvironment communications?. Cancer Commun (Lond). 2022;42(2):83-87. doi:10.1002/cac2.12257
• 15. Gu Q, Wang Y, Yi P, Cheng C. Theoretical framework and emerging challenges of lipid metabolism in cancer. Semin Cancer Biol. 2025;108:48-70. doi:10.1016/j.semcancer.2024.12.002
• 16. Fu Y, Zou T, Shen X, et al. Lipid metabolism in cancer progression and therapeutic strategies. MedComm. 2020;2(1):27-59. doi:10.1002/mco2.27
• 17. Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021;218(1):e20201606. doi:10.1084/jem.20201606
• 18. Liu Q, Luo Q, Halim A, Song G. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer. Cancer Lett. 2017;401:39-45. doi:10.1016/j.canlet.2017.05.002
• 19. Broadfield LA, Pane AA, Talebi A, Swinnen JV, Fendt SM. Lipid metabolism in cancer: New perspectives and emerging mechanisms. Dev Cell. 2021;56(10):1363-1393. doi:10.1016/j.devcel.2021.04.013
• 20. Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4-22. doi:10.1038/s41416-019-0650-z
• 21. Cheng C, Geng F, Cheng X, Guo D. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond). 2018;38(1):27. doi:10.1186/s40880-018-0301-4
• 22. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016;2(5):e1600200. doi:10.1126/sciadv.1600200
• 23. Petan T. Lipid Droplets in Cancer. Rev Physiol Biochem Pharmacol. 2023;185:53-86. doi:10.1007/112_2020_51
• 24. Walther TC, Chung J, Farese RV Jr. Lipid Droplet Biogenesis. Annu Rev Cell Dev Biol. 2017;33:491-510. doi:10.1146/annurev-cellbio-100616-060608
• 25. Zadoorian A, Du X, Yang H. Lipid droplet biogenesis and functions in health and disease. Nat Rev Endocrinol. 2023;19(8):443-459. doi:10.1038/s41574-023-00845-0
• 26. Cruz ALS, Barreto EA, Fazolini NPB, Viola JPB, Bozza PT. Lipid droplets: platforms with multiple functions in cancer hallmarks. Cell Death Dis. 2020;11(2):105. doi:10.1038/s41419-020-2297-3
• 27. Luo W, Wang H, Ren L, et al. Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression. Int J Biol Sci. 2022;18(16):6020-6034. doi:10.7150/ijbs.74902
• 28. Pagliari F, Jansen J, Knoll J, Hanley R, Seco J, Tirinato L. Cancer radioresistance is characterized by a differential lipid droplet content along the cell cycle. Cell Div. 2024;19(1):14. doi:10.1186/s13008-024-00116-y
• 29. Chao H, Deng L, Xu F, et al. MEX3C regulates lipid metabolism to promote bladder tumorigenesis through JNK pathway. Onco Targets Ther. 2019;12:3285-3294. doi:10.2147/OTT.S199667
• 30. Lorito N, Subbiani A, Smiriglia A, et al. FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer. EMBO Mol Med. 2024;16(7):1533-1559. doi:10.1038/s44321-024-00090-6
• 31. Pham DV, Park PH. Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming. J Exp Clin Cancer Res. 2022;41(1):9. doi:10.1186/s13046-021-02223-y
• 32. Tirinato L, Liberale C, Di Franco S, et al. Lipid droplets: a new player in colorectal cancer stem cells unveiled by spectroscopic imaging. Stem Cells. 2015;33(1):35-44. doi:10.1002/stem.1837
• 33. Shen C, Liu J, Liu H, et al. Timosaponin AIII induces lipid peroxidation and ferroptosis by enhancing Rab7-mediated lipophagy in colorectal cancer cells. Phytomedicine. 2024;122:155079. doi:10.1016/j.phymed.2023.155079
• 34. Cotte AK, Aires V, Fredon M, et al. Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance. Nat Commun. 2018;9(1):322. doi:10.1038/s41467-017-02732-5
• 35. Zhang CY, Zhang R, Zhang L, et al. Regenerating gene 4 promotes chemoresistance of colorectal cancer by affecting lipid droplet synthesis and assembly. World J Gastroenterol. 2023;29(35):5104-5124. doi:10.3748/wjg.v29.i35.5104
• 36. Zhao Z, Wang J, Kong W, et al. Palmitic Acid Exerts Anti-Tumorigenic Activities by Modulating Cellular Stress and Lipid Droplet Formation in Endometrial Cancer. Biomolecules. 2024;14(5):601. doi:10.3390/biom14050601
• 37. Deng B, Kong W, Suo H, et al. Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer. Cancers (Basel). 2023;15(22):5407. doi:10.3390/cancers15225407
• 38. Coates HW, Nguyen TB, Du X, et al. The constitutively active form of a key cholesterol synthesis enzyme is lipid droplet-localized and upregulated in endometrial cancer tissues. J Biol Chem. 2024;300(5):107232. doi:10.1016/j.jbc.2024.107232
• 39. Zhou T, Li X, Zhao F, Zhou J, Sun B. Lactamase β reprograms lipid metabolism to inhibit the progression of endometrial cancer through attenuating MDM2-mediated p53 ubiquitination and degradation. Arch Biochem Biophys. 2025;764:110287. doi:10.1016/j.abb.2024.110287
• 40. Kou Y, Geng F, Guo D. Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage. Biomedicines. 2022;10(8):1943. doi:10.3390/biomedicines10081943
• 41. Cheng X, Geng F, Pan M, et al. Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress. Cell Metab. 2020;32(2):229-242.e8. doi:10.1016/j.cmet.2020.06.002
• 42. Taïb, B., Aboussalah, A.M., Moniruzzaman, M. et al. Lipid accumulation and oxidation in glioblastoma multiforme. Sci Rep. 2019;9(1):19593. doi:10.1038/s41598-019-55985-z
• 43. Nakagawa H, Hayata Y, Kawamura S, Yamada T, Fujiwara N, Koike K. Lipid Metabolic Reprogramming in Hepatocellular Carcinoma. Cancers (Basel). 2018;10(11):447. doi:10.3390/cancers10110447
• 44. Wu C, Dai C, Li X, et al. AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy. Theranostics. 2022;12(18):7681-7698. doi:10.7150/thno.74974
• 45. Jin C, Yuan P. Implications of lipid droplets in lung cancer: Associations with drug resistance. Oncol Lett. 2020;20(3):2091-2104. doi:10.3892/ol.2020.11769
• 46. Yang T, Qiao S, Zhu X. High-dose radiation-resistant lung cancer cells stored many functional lipid drops through JAK2/p-STAT3/FASN pathway. J Cancer Res Clin Oncol. 2023;149(15):14169-14183. doi:10.1007/s00432-023-05106-1
• 47. Bai R, Rebelo A, Kleeff J, Sunami Y. Identification of prognostic lipid droplet-associated genes in pancreatic cancer patients via bioinformatics analysis. Lipids Health Dis. 2021;20(1):58. doi:10.1186/s12944-021-01476-y
• 48. Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol. 2021;18(7):493-502. doi:10.1038/s41575-021-00457-x
• 49. Sahin, S, Ozensoy Guler, O, Sunguroglu, A, Ercin, ME., Atakol, D, Kilic, HA, Kilic Dener, E, Simsek, E. Analysis of the effects of BZO HEXOXIZID (MDA19) on the expression level of PLA2G7, UCP2 and NEDD4L proteins in prostate cancer cells. World Academy of Sciences Journal, 2025;7:45. doi:10.3892/wasj.2025.333
• 50. Deep G, Schlaepfer IR. Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis. Int J Mol Sci. 2016;17(7):1061. doi:10.3390/ijms17071061
• 51. Butler LM, Centenera MM, Swinnen JV. Androgen control of lipid metabolism in prostate cancer: novel insights and future applications. Endocr Relat Cancer. 2016;23(5):R219-R227. doi:10.1530/ERC-15-0556
• 52. Atakol D, Özensoy Güler Ö, Terzi E, Yılmaz H, Ercin ME, Şimşek E. Investigation of Protein Expressions of PLA2G7, UCP2 and NEDD4L Genes Associated with Fat Droplet Formation in Prostate Cancer. OTSBD. 2023;8(4):497-502. doi:10.26453/otjhs.1330334
• 53. Hadjmimoune A, Çarhan A, Öz Bedir BE, Yılmaz H, Ercın ME, Şimşek E. The Effect of Thymoquinone on the Protein Levels of PLA2G7, UCP2, and NEDD4L Genes Associated with Lipid Droplets Formation in Prostate Cancer. OTSBD. 2024;9(1):97-102. doi:10.26453/otjhs.1422576
• 54. Zhou J, Simon JM, Liao C, et al. An oncogenic JMJD6-DGAT1 axis tunes the epigenetic regulation of lipid droplet formation in clear cell renal cell carcinoma. Mol Cell. 2022;82(16):3030-3044.e8. doi:10.1016/j.molcel.2022.06.003
• 55. Klasson TD, LaGory EL, Zhao H, et al. ACSL3 regulates lipid droplet biogenesis and ferroptosis sensitivity in clear cell renal cell carcinoma. Cancer Metab. 2022;10(1):14. doi:10.1186/s40170-022-00290-z
• 56. Sainero-Alcolado L, Garde-Lapido E, Snaebjörnsson MT, et al. Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma. Proc Natl Acad Sci U S A. 2024;121(7):e2310479121. doi:10.1073/pnas.2310479121
• 57. Hayakawa M, Taylor JN, Nakao R, et al. Lipid droplet accumulation and adipophilin expression in follicular thyroid carcinoma. Biochem Biophys Res Commun. 2023;640:192-201. doi:10.1016/j.bbrc.2022.12.007