Skip to main content

The Role of Lipid Metabolism in the Development of Lung Cancer

  • Chapter
  • First Online:
Lipidomics in Health & Disease

Part of the book series: Translational Bioinformatics ((TRBIO,volume 14))

Abstract

The increase of lipid synthesis in tumor tissues has been considered as an important component of substance and energy metabolism during cell transformation. In recent years, the role of lipids in the transformation of cells into tumors, tumor growth, invasion and metastasis have attracted much attention. This article reviews the effects of lipid metabolism related enzymes, membrane lipids and extracellular environment on the development of lung cancer. Finally, the application of lipid metabolism related drugs in lung cancer was briefly summarized.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Reference

  • Aragane K, Tamai Y, Kusunoki J. Hepatic de novo lipogenesis is present in liver-specific ACC1-deficient mice. Mol Cell Biol. 2007;27(5):1881–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9):170070.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brown M, Roulson J-A, Hart CA, Tawadros T, Clarke NW. Arachidonic acid induction of Rho-mediated transendothelial migration in prostate cancer. Br J Cancer. 2014;110(8):2099–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byagowi S, NaserpourFarivar T, Najafipour R. Effect of PPARd agonist on stearoyl-CoA desaturase 1 in human pancreatic cancer cells: role of MEK/ERK1/2 pathway. Can J Diabetes. 2015;39(2):123–7.

    Article  PubMed  Google Scholar 

  • Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer. 2013;13(4):227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W-C, Wang C-Y, Hung Y-H, Weng T-Y, Yen M-C, Lai M-D. Systematic analysis of gene expression alterations and clinical outcomes for long-chain acyl-coenzyme A synthetase family in cancer. Shridhar V, ed. PLoS One. 2016;11(5):e0155660.

    Google Scholar 

  • Corti F, Finetti F, Ziche M, Simons M. The syndecan-4/protein kinase Cα pathway mediates prostaglandin E2-induced extracellular regulated kinase (ERK) activation in endothelial cells and angiogenesis in vivo. J Biol Chem. 2013;288(18):12712–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csanadi A, Kayser C, Donauer M. Prognostic value of malic enzyme and ATP-citrate lyase in non-small cell lung cancer of the young and the elderly. PLoS One. 2015;10(5):e0126357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daniëls VW, Smans K, Royaux I, Chypre M, Swinnen JV, Zaidi N. Cancer cells differentially activate and thrive on de novo lipid synthesis pathways in a low-lipid environment. Lobaccaro J-MA, ed. PLoS One. 2014; 9(9):e106913.

    Google Scholar 

  • Dayal R, Singh A, Pandey A, Mishra KP. Reactive oxygen species as mediator of tumor radiosensitivity. J Cancer Res Ther. 2014;10(4):811–8.

    Article  PubMed  Google Scholar 

  • Eichmann TO, Lass A. DAG tales: the multiple faces of diacylglycerol—stereochemistry, metabolism, and signaling. Cell Mol Life Sci, CMLS. 2015;72(20):3931–52.

    Article  CAS  PubMed  Google Scholar 

  • Fan J, Kamphorst JJ, Mathew R, et al. Glutamine-driven oxidative phosphorylation is a major ATP source in transformed mammalian cells in both normoxia and hypoxia. Mol Syst Biol. 2013;9:712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foster DA. Phosphatidic acid and lipid sensing by mTOR. Trends Endocrinol Metab. 2013;24(6):272–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu QF, Liu Y, Fan Y, Hua SN, Qu HY, Dong SW, et al. Alpha-enolase promotes cell glycolysis, growth, migration, and invasion in non-small cell lung cancer through FAK-mediated PI3K/AKT pathway. J Hematol Oncol. 2015;8:22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldkorn T, Chung S, Filosto S. Lung cancer and lung injury: the dual role of ceramide. Handb Exp Pharmacol. 2013;216:93–113.

    Article  CAS  Google Scholar 

  • Gómez de Cedrón M, Ramírez de Molina A. Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism. J Lipid Res. 2016;57(2):193–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo JY, Karsli-Uzunbas G, Mathew R. Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev. 2013;27(13):1447–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hess D, Chisholm JW, Igal RA. Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells. PLoS One. 2010;5(6):e11394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopperton KE, Duncan RE, Bazinet RP, Archer MC. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity. Exp Cell Res. 2014;320(2):302–10.

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Freter C. Lipid metabolism, apoptosis and cancer therapy. Lemarié A, ed. Int J Mol Sci 2015; 16(1):924–949.

    Google Scholar 

  • Huang S-W, Kao J-K, Wu C-Y, et al. Targeting aerobic glycolysis and HIF-1α expression enhance Imiquimod-induced apoptosis in cancer cells. Oncotarget. 2014;5(5):1363–81.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang J, Fan X-X, He J, et al. SCD1 is associated with tumor promotion, late stage and poor survival in lung adenocarcinoma. Oncotarget. 2016;7(26):39970–9.

    PubMed  PubMed Central  Google Scholar 

  • Jeon S-M, Chandel NS, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature. 2012;485(7400):661–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jerby L, Wolf L, Denkert C, et al. Metabolic associations of reduced proliferation and oxidative stress in advanced breast cancer. Cancer Res. 2012;72(22):5712–20.

    Article  CAS  PubMed  Google Scholar 

  • Jiang L, Wang H, Li J, et al. Up-regulated FASN expression promotes Transcoelomic metastasis of ovarian cancer cell through epithelial-mesenchymal transition. Int J Mol Sci. 2014;15(7):11539–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamphorst JJ, Cross JR, Fan J. Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci U S A. 2013;110(22):8882–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Knobloch M, Braun SM, Zurkirchen L, et al. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature. 2013;493(7431):226–30.

    Article  CAS  PubMed  Google Scholar 

  • Knoch F, Tarantola M, Bodenschatz E, Rappel W-J. Modeling self-organized spatio-temporal patterns of PIP3 and PTEN during spontaneous cell polarization. Phys Biol. 2014;11(4):046002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kopf T, Schaefer H-L, Troetzmueller M, et al. Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats. Oresic M, ed. PLoS One. 2014; 9(9):e106849.

    Google Scholar 

  • Książek M, ChaciÅ„ska M, Chabowski A, Baranowski M. Sources, metabolism, and regulation of circulating sphingosine-1-phosphate. J Lipid Res. 2015;56(7):1271–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuhajda FP, Jenner K, Wood FD, et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci U S A. 1994;91(14):6379–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin R, Tao R, Gao X, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013;51(4):506–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medes G, Thomas A, Weinhouse S. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res. 1953;13:27–9.

    PubMed  CAS  Google Scholar 

  • Menendez JA, Lupu R. Fatty acid synthase regulates estrogen receptor-α signaling in breast cancer cells. Oncogene. 2017;6(2):e299.

    Article  CAS  Google Scholar 

  • Mojumdar EH, Helder RW, Gooris GS, Bouwstra JA. Monounsaturated fatty acids reduce the barrier of stratum corneum lipid membranes by enhancing the formation of a hexagonal lateral packing. Langmuir. 2014;30(22):6534–43.

    Article  CAS  PubMed  Google Scholar 

  • Montagne K, Uchiyama H, Furukawa KS, Ushida T. Hydrostatic pressure decreases membrane fluidity and lipid desaturase expression in chondrocyte progenitor cells. J Biomech. 2014;47(2):354–9.

    Article  PubMed  Google Scholar 

  • Muro E, Atilla-Gokcumen GE, Eggert US. Lipids in cell biology: how can we understand them better? Bement W, ed. Mol Biol Cell 2014; 25(12):1819–1823.

    Google Scholar 

  • Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia. 2015;3:83–92.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nashed M, Chisholm JW, Igal RA. Stearoyl-CoA desaturase activity modulates the activation of epidermal growth factor receptor in human lung cancer cells. Exp Biol Med (Maywood). 2012;237(9):1007–17.

    Article  CAS  Google Scholar 

  • O’Neill HM, Lally JS, Galic S, et al. AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia. 2014;57(8):1693–702.

    Article  CAS  PubMed  Google Scholar 

  • Padanad MS, Konstantinidou G, Venkateswaran N, et al. Fatty acid oxidation mediated by Acyl-CoA synthetase long chain 3 is required for mutant KRAS lung tumorigenesis. Cell Rep. 2016;16(6):1614–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parsons JB, Rock CO. Bacterial lipids: metabolism and membrane homeostasis. Prog Lipid Res. 2013;52(3):249–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pisanu ME, Noto A, De Vitis C, et al. Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett. 2017;406:93–104.

    Article  CAS  PubMed  Google Scholar 

  • Prior AM, Zhang M, Blakeman N, et al. Inhibition of long chain fatty Acyl-CoA Synthetase (ACSL) and ischemia reperfusion injury. Bioorg Med Chem Lett. 2014;24(4):1057–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiang L, Kon N, Zhao W, et al. Hepatic SirT1-dependent gain-of-function of stearoyl-CoA desaturase-1 conveys dysmetabolic and tumor progression functions. Cell Rep. 2015;11(11):1797–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Relat J, Blancafort A, Oliveras G. Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer. BMC Cancer. 2012;12:280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riaz A, Huang Y, Johansson S. G-protein-coupled lysophosphatidic acid receptors and their regulation of AKT signaling. Van Craenenbroeck K, Tikkanen R, eds. Int J Mol Sci. 2016;17(2):215.

    Google Scholar 

  • Sampath H, Ntambi JM. Role of stearoyl-CoA desaturase-1 in skin integrity and whole body energy balance. J Biol Chem. 2014;289(5):2482–8.

    Article  CAS  PubMed  Google Scholar 

  • Schuster B, Sleytr UB. Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules. J R Soc Interface. 2014;11(96):20140232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi J, Yang H, Duan X, Li L, Sun L, Li Q, et al. Apolipoproteins as differentiating and predictive markers for assessing clinical outcomes in patients with small cell lung Cancer. Yonsei Med J. 2016;57(3):549–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simopoulos AP. An increase in the Omega-6/Omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016;8(3):128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sounni NE, Cimino J, Blacher S, et al. Blocking lipid synthesis overcomes tumor regrowth and metastasis after antiangiogenic therapy withdrawal. Cell Metab. 2014;20(2):280–94.

    Article  CAS  PubMed  Google Scholar 

  • Svensson RU, Parker SJ, Eichner LJ, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small cell lung cancer in preclinical models. Nat Med. 2016;22(10):1108–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ventura R, Mordec K, Waszczuk J. Inhibition of de novo palmitate synthesis by fatty acid synthase induces apoptosis in tumor cells by remodeling cell membranes, inhibiting signaling pathways, and reprogramming gene expression. EBioMedicine. 2015;2(8):808–24.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Zhang X, Tan W, Fu J, Zhang W. Significance of fatty acid synthase expression in non-small cell lung cancer. Zhonghuazhongliuzazhi [Chin J Oncol]. 2002;24(3):271–3.

    CAS  Google Scholar 

  • White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 2012;12(6):401–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanaka M, Tian Z, Darvish-Ghane S, Zhuo M. Pre-LTP requires extracellular signal-regulated kinase in the ACC. Mol Pain. 2016;12:174480691664737.

    Article  CAS  Google Scholar 

  • Yamashita T, Kamada H, Kanasaki S, et al. Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Pharmazie. 2013;68(12):969–73.

    PubMed  CAS  Google Scholar 

  • Yan S, Yang X-F, Liu H-L, Fu N, Ouyang Y, Qing K. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol, WJG. 2015;21(12):3492–8.

    Article  CAS  PubMed  Google Scholar 

  • Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res. 2012;72:3709–14.

    Article  CAS  PubMed  Google Scholar 

  • Zaugg K, Yao Y, Reilly PT, et al. Carnitinepalmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev. 2011;25(10):1041–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Wang H, Zhang J, et al. Positive feedback loop and synergistic effects between hypoxia-inducible factor-2α and stearoyl-CoA desaturase-1 promote tumorigenesis in clear cell renal cell carcinoma. Cancer Sci. 2013;104(4):416–22.

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Song F, Zhao X, et al. EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer. Mol Cancer. 2017;16:127.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zordoky BN, Nagendran J, Pulinilkunnil T. AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circ Res. 2014;115(5):518–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiu-Min Li .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wang, L., Huang, W., Li, XM. (2018). The Role of Lipid Metabolism in the Development of Lung Cancer. In: Wang, X., Wu, D., Shen, H. (eds) Lipidomics in Health & Disease. Translational Bioinformatics, vol 14. Springer, Singapore. https://doi.org/10.1007/978-981-13-0620-4_2

Download citation

Publish with us

Policies and ethics