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Fatty acid metabolism and cancer development

脂肪酸代谢与癌症发生

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  • Life & Medical Sciences
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Science Bulletin

Abstract

Although the type and etiology of cancers are different, pathways in glucose metabolism, pentose phosphate pathway (PPP) and glutamine metabolism have been reprogrammed in cancer cells to adapt to their rapid growth and proliferation. Recent research has also shown that multiple lipid metabolic pathways are altered in cancer cells. Here, we provide a brief review for the role of fatty acid metabolism in cancer development with a special focus on fatty acid uptake and de novo synthesis, triglycerides synthesis, storage and degradation. Reprogramming in fatty acid metabolism plays important roles in providing energy, macromolecules for membrane synthesis and lipid signals during cancer development. Understanding the mechanism of deregulated lipid metabolic pathways in cancer cells would reveal novel therapeutic approaches to combat cancer.

摘要

虽然癌症类型和病因各有不同,但是癌细胞中代谢通路的变化却有一定的相似性,葡萄糖代谢途径、磷酸戊糖途径和谷氨酰胺代谢途径都发生变化来适应癌细胞的快速生长和增殖。最近的研究表明,许多脂肪酸代谢途径在癌细胞中也发生了改变。这里我们主要从脂肪酸的吸收、合成,甘油三酯合成、储存和降解等几方面总结了关于脂肪酸代谢途径变化与癌症发生关系的相关研究结果。在癌症发展过程中,脂肪酸代谢通路的变化为癌症的发生和发展提供能量、生物膜大分子以及信号分子等方面扮演重要角色。了解肿瘤细胞中脂肪酸代谢通路变化有助于为癌症治疗的治疗提供新方法。

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References

  1. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Metallo CM, Gameiro PA, Bell EL et al (2012) Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481:380–384

    ADS  CAS  Google Scholar 

  3. Furuhashi M, Hotamisligil GS (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 7:489–503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hotamisligil GS, Bernlohr DA (2015) Metabolic functions of FABPs-mechanisms and therapeutic implications. Nat Rev Endocrinol 11:592–605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Farese RV Jr, Walther TC (2009) Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 139:855–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Walther TC, Farese RV Jr (2012) Lipid droplets and cellular lipid metabolism. Annu Rev Biochem 81:687–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ye J, DeBose-Boyd RA (2011) Regulation of cholesterol and fatty acid synthesis. Cold Spring Harb Perspect Biol 3:a004754

    Article  PubMed  PubMed Central  Google Scholar 

  9. Worgall TS (2008) Regulation of lipid metabolism by sphingolipids. Subcell Biochem 49:371–385

    Article  PubMed  Google Scholar 

  10. Currie E, Schulze A, Zechner R et al (2013) Cellular fatty acid metabolism and cancer. Cell Metab 18:153–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Thumser AE, Moore JB, Plant NJ (2014) Fatty acid binding proteins: tissue-specific functions in health and disease. Curr Opin Clin Nutr Metab Care 17:124–129

    Article  CAS  PubMed  Google Scholar 

  12. Liu RZ, Graham K, Glubrecht DD et al (2011) Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy. Am J Pathol 178:997–1008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Adamson J, Morgan EA, Beesley C et al (2003) High-level expression of cutaneous fatty acid-binding protein in prostatic carcinomas and its effect on tumorigenicity. Oncogene 22:2739–2749

    Article  CAS  PubMed  Google Scholar 

  14. Levi L, Wang Z, Doud MK et al (2015) Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5. Nat Commun 6:8794

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kawaguchi K, Kinameri A, Suzuki S et al (2016) The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis. Biochem J 473:449–461

    Article  CAS  PubMed  Google Scholar 

  16. Hotamisligil GS, Johnson RS, Distel RJ et al (1996) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274:1377–1379

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Nieman KM, Kenny HA, Penicka CV et al (2011) Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 17:1498–1503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bensaad K, Favaro E, Lewis CA et al (2014) Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep 9:349–365

    Article  CAS  PubMed  Google Scholar 

  19. Hale JS, Otvos B, Sinyuk M et al (2014) Cancer stem cell-specific scavenger receptor 36 drives glioblastoma progression. Stem Cells 32:1746–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liang Y, Diehn M, Watson N et al (2005) Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proc Natl Acad Sci USA 102:5814–5819

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. Santos CR, Schulze A (2012) Lipid metabolism in cancer. FEBS J 279:2610–2623

    Article  CAS  PubMed  Google Scholar 

  22. Menendez JA, Lupu R (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 7:763–777

    Article  CAS  PubMed  Google Scholar 

  23. Mashima T, Seimiya H, Tsuruo T (2009) De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br J Cancer 100:1369–1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Esslimani-Sahla M, Thezenas S, Simony-Lafontaine J et al (2007) Increased expression of fatty acid synthase and progesterone receptor in early steps of human mammary carcinogenesis. Int J Cancer 120:224–229

    Article  CAS  PubMed  Google Scholar 

  25. Sadowski MC, Pouwer RH, Gunter JH et al (2014) The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer. Oncotarget 5:9362–9381

    Article  PubMed  PubMed Central  Google Scholar 

  26. Khwairakpam AD, Shyamananda MS, Sailo BL et al (2015) ATP citrate lyase (ACLY): a promising target for cancer prevention and treatment. Curr Drug Targets 16:156–163

    Article  CAS  PubMed  Google Scholar 

  27. Beckers A, Organe S, Timmermans L et al (2007) Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells. Cancer Res 67:8180–8187

    Article  CAS  PubMed  Google Scholar 

  28. Sun Y, He W, Luo M et al (2015) SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through targeting lipid metabolism. Tumour Biol 36:4133–4141

    Article  CAS  PubMed  Google Scholar 

  29. Williams KJ, Argus JP, Zhu Y et al (2013) An essential requirement for the SCAP/SREBP signaling axis to protect cancer cells from lipotoxicity. Cancer Res 73:2850–2862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lewis CA, Brault C, Peck B et al (2015) SREBP maintains lipid biosynthesis and viability of cancer cells under lipid- and oxygen-deprived conditions and defines a gene signature associated with poor survival in glioblastoma multiforme. Oncogene 34:5128–5140

    Article  CAS  PubMed  Google Scholar 

  31. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785

    Article  CAS  PubMed  Google Scholar 

  32. Zadra G, Photopoulos C, Tyekucheva S et al (2014) A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med 6:519–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. O’Brien AJ, Villani LA, Broadfield LA et al (2015) Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochem J 469:177–187

    Article  PubMed  Google Scholar 

  34. Cully M, You H, Levine AJ et al (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6:184–192

    Article  CAS  PubMed  Google Scholar 

  35. Porstmann T, Griffiths B, Chung YL et al (2005) PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP. Oncogene 24:6465–6481

    CAS  PubMed  Google Scholar 

  36. Shao W, Espenshade PJ (2012) Expanding roles for SREBP in metabolism. Cell Metab 16:414–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Porstmann T, Santos CR, Griffiths B et al (2008) SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab 8:224–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Watkins PA (1997) Fatty acid activation. Prog Lipid Res 36:55–83

    Article  CAS  PubMed  Google Scholar 

  39. Bozza PT, Viola JP (2010) Lipid droplets in inflammation and cancer. Prostaglandins Leukot Essent Fatty Acids 82:243–250

    Article  CAS  PubMed  Google Scholar 

  40. Monaco ME, Creighton CJ, Lee P et al (2010) Expression of long-chain fatty Acyl-CoA synthetase 4 in breast and prostate cancers is associated with sex steroid hormone receptor negativity. Transl Oncol 3:91–98

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sung YK, Park MK, Hong SH et al (2007) Regulation of cell growth by fatty acid-CoA ligase 4 in human hepatocellular carcinoma cells. Exp Mol Med 39:477–482

    Article  CAS  PubMed  Google Scholar 

  42. Sun P, Xia S, Lal B et al (2014) Lipid metabolism enzyme ACSVL3 supports glioblastoma stem cell maintenance and tumorigenicity. BMC Cancer 14:401

    Article  PubMed  PubMed Central  Google Scholar 

  43. Vargas T, Moreno-Rubio J, Herranz J et al (2015) ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients. Oncotarget 6:7348–7363

    Article  PubMed  PubMed Central  Google Scholar 

  44. Diefenbach CS, Soslow RA, Iasonos A et al (2006) Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival. Cancer 107:1511–1519

    Article  CAS  PubMed  Google Scholar 

  45. Mansilla F, da Costa KA, Wang S et al (2009) Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer. J Mol Med (Berl) 87:85–97

    Article  CAS  Google Scholar 

  46. Agarwal AK, Garg A (2010) Enzymatic activity of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 11: upregulated in breast and cervical cancers. J Lipid Res 51:2143–2152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pellon-Maison M, Montanaro MA, Lacunza E et al (2014) Glycerol-3-phosphate acyltranferase-2 behaves as a cancer testis gene and promotes growth and tumorigenicity of the breast cancer MDA-MB-231 cell line. PLoS ONE 9:e100896

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  48. Accioly MT, Pacheco P, Maya-Monteiro CM et al (2008) Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells. Cancer Res 68:1732–1740

    Article  CAS  PubMed  Google Scholar 

  49. Tirinato L, Liberale C, Di Franco S et al (2015) Lipid droplets: a new player in colorectal cancer stem cells unveiled by spectroscopic imaging. Stem Cells 33:35–44

    Article  CAS  PubMed  Google Scholar 

  50. Abramczyk H, Surmacki J, Kopec M et al (2015) The role of lipid droplets and adipocytes in cancer. Raman imaging of cell cultures: MCF10A, MCF7, and MDA-MB-231 compared to adipocytes in cancerous human breast tissue. Analyst 140:2224–2235

    Article  ADS  CAS  PubMed  Google Scholar 

  51. Kuemmerle NB, Rysman E, Lombardo PS et al (2011) Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol Cancer Ther 10:427–436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Carter SA, Foster NA, Scarpini CG et al (2012) Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus. Br J Cancer 107:739–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Van Bockstaele F, Pede V, Janssens A et al (2007) Lipoprotein lipase mRNA expression in whole blood is a prognostic marker in B cell chronic lymphocytic leukemia. Clin Chem 53:204–212

    Article  PubMed  Google Scholar 

  54. Maloum K, Settegrana C, Chapiro E et al (2009) IGHV gene mutational status and LPL/ADAM29 gene expression as clinical outcome predictors in CLL patients in remission following treatment with oral fludarabine plus cyclophosphamide. Ann Hematol 88:1215–1221

    Article  CAS  PubMed  Google Scholar 

  55. Kaderi MA, Kanduri M, Buhl AM et al (2011) LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia. Haematologica 96:1153–1160

    Article  PubMed  PubMed Central  Google Scholar 

  56. Young SG, Zechner R (2013) Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev 27:459–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yang X, Lu X, Lombes M et al (2010) The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab 11:194–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Welch C, Santra MK, El-Assaad W et al (2009) Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer Res 69:6782–6789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ou J, Miao H, Ma Y et al (2014) Loss of abhd5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition. Cell Rep 9:1798–1811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zechner R (2015) FAT FLUX: enzymes, regulators, and pathophysiology of intracellular lipolysis. EMBO Mol Med 7:359–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nomura DK, Long JZ, Niessen S et al (2010) Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 140:49–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Nomura DK, Lombardi DP, Chang JW et al (2011) Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem Biol 18:846–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ryden M, Agustsson T, Laurencikiene J et al (2008) Lipolysis–not inflammation, cell death, or lipogenesis–is involved in adipose tissue loss in cancer cachexia. Cancer 113:1695–1704

    Article  PubMed  Google Scholar 

  64. Strassmann G, Fong M, Freter CE et al (1993) Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. J Clin Invest 92:2152–2159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tsoli M, Schweiger M, Vanniasinghe AS et al (2014) Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation. PLoS ONE 9:e92966

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  66. Das SK, Eder S, Schauer S et al (2011) Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333:233–238

    Article  ADS  CAS  PubMed  Google Scholar 

  67. Arner P, Langin D (2014) Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance. Trends Endocrinol Metab 25:255–262

    Article  CAS  PubMed  Google Scholar 

  68. Iorio E, Ricci A, Bagnoli M et al (2010) Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells. Cancer Res 70:2126–2135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ramirez de Molina A, Rodriguez-Gonzalez A, Gutierrez R et al (2002) Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 296:580–583

    Article  CAS  PubMed  Google Scholar 

  70. Glunde K, Bhujwalla ZM, Ronen SM (2011) Choline metabolism in malignant transformation. Nat Rev Cancer 11:835–848

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Luevano-Martinez LA, Kowaltowski AJ (2015) Phosphatidylglycerol-derived phospholipids have a universal, domain-crossing role in stress responses. Arch Biochem Biophys 585:90–97

    Article  CAS  PubMed  Google Scholar 

  72. Eichmann TO, Lass A (2015) DAG tales: the multiple faces of diacylglycerol–stereochemistry, metabolism, and signaling. Cell Mol Life Sci 72:3931–3952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mills GB, Moolenaar WH (2003) The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 3:582–591

    Article  CAS  PubMed  Google Scholar 

  74. Aikawa S, Hashimoto T, Kano K et al (2015) Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem 157:81–89

    Article  CAS  PubMed  Google Scholar 

  75. Samudio I, Harmancey R, Fiegl M et al (2010) Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 120:142–156

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank members of the P.L. Laboratory at Tsinghua University for helpful discussion. This work was supported by the National Basic Research Program (2013CB530602), and the National Natural Science Foundation of China (31430040, 31321003).

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  1. MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China

    Yuanying Chen & Peng Li

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  1. Yuanying Chen
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Correspondence to Peng Li.

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SPECIAL TOPIC: Lipid metabolism and human metabolic disorder

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Chen, Y., Li, P. Fatty acid metabolism and cancer development. Sci. Bull. 61, 1473–1479 (2016). https://doi.org/10.1007/s11434-016-1129-4

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  • DOI: https://doi.org/10.1007/s11434-016-1129-4

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