Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development

DMM Disease Models and Mechanisms - Tập 6 Số 6 - Trang 1353-1363 - 2013
Franziska Baenke1, Barrie Peck1, Heike Miess1, Almut Schulze1
1Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK

Tóm tắt

An increased rate of lipid synthesis in cancerous tissues has long been recognised as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids to cellular transformation, tumour development and tumour progression, as well as their potential role in facilitating the spread of cancerous cells to secondary sites, are not yet fully understood. In this article, we review the recent findings that support the importance of lipid synthesis and metabolism in tumorigenesis. Specifically, we explore the role of aberrant lipid biosynthesis in cancer cell migration and invasion, and in the induction of tumour angiogenesis. These processes are crucial for the dissemination of tumour cells and formation of metastases, which constitute the main cause of cancer mortality.

Từ khóa


Tài liệu tham khảo

Abramson, 2011, The lipogenesis pathway as a cancer target, J. Med. Chem., 54, 5615, 10.1021/jm2005805

Alli, 2005, Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice, Oncogene, 24, 39, 10.1038/sj.onc.1208174

Ariyama, 2010, Decrease in membrane phospholipid unsaturation induces unfolded protein response, J. Biol. Chem., 285, 22027, 10.1074/jbc.M110.126870

Bauer, 2005, ATP citrate lyase is an important component of cell growth and transformation, Oncogene, 24, 6314, 10.1038/sj.onc.1208773

Beckers, 2007, Chemical inhibition of acetyl-CoA carboxylase induces growth arrest and cytotoxicity selectively in cancer cells, Cancer Res., 67, 8180, 10.1158/0008-5472.CAN-07-0389

Bengoechea-Alonso, 2007, SREBP in signal transduction: cholesterol metabolism and beyond, Curr. Opin. Cell Biol., 19, 215, 10.1016/j.ceb.2007.02.004

Berwick, 2002, The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes, J. Biol. Chem., 277, 33895, 10.1074/jbc.M204681200

Carling, 1989, Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities, Eur. J. Biochem., 186, 129, 10.1111/j.1432-1033.1989.tb15186.x

Chang, 2004, Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression, Proc. Natl. Acad. Sci. USA, 101, 591, 10.1073/pnas.2535911100

Clendening, 2010, Dysregulation of the mevalonate pathway promotes transformation, Proc. Natl. Acad. Sci. USA, 107, 15051, 10.1073/pnas.0910258107

Dall’Armi, 2013, The role of lipids in the control of autophagy, Curr. Biol., 23, R33, 10.1016/j.cub.2012.10.041

Denko, 2008, Hypoxia, HIF1 and glucose metabolism in the solid tumour, Nat. Rev. Cancer, 8, 705, 10.1038/nrc2468

Düvel, 2010, Activation of a metabolic gene regulatory network downstream of mTOR complex 1, Mol. Cell, 39, 171, 10.1016/j.molcel.2010.06.022

Ecker, 2010, Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes, Proc. Natl. Acad. Sci. USA, 107, 7817, 10.1073/pnas.0912059107

Emberson, 2012, Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy, PLoS ONE, 7, e29849, 10.1371/journal.pone.0029849

Ettinger, 2004, Dysregulation of sterol response element-binding proteins and downstream effectors in prostate cancer during progression to androgen independence, Cancer Res., 64, 2212, 10.1158/0008-5472.CAN-2148-2

Freed-Pastor, 2012, Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway, Cell, 148, 244, 10.1016/j.cell.2011.12.017

Friedl, 2003, Tumour-cell invasion and migration: diversity and escape mechanisms, Nat. Rev. Cancer, 3, 362, 10.1038/nrc1075

Fritz, 2010, Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice, Mol. Cancer Ther., 9, 1740, 10.1158/1535-7163.MCT-09-1064

Furuta, 2008, Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1, Cancer Res., 68, 1003, 10.1158/0008-5472.CAN-07-2489

Griffiths, 2013, Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumour growth, Cancer Metab., 1, 3, 10.1186/2049-3002-1-3

Guo, 2009, EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy, Sci. Signal., 2, ra82, 10.1126/scisignal.2000446

Guo, 2011, Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis, Genes Dev., 25, 460, 10.1101/gad.2016311

Hager, 2006, The role of cholesterol in prostate cancer, Curr. Opin. Clin. Nutr. Metab. Care, 9, 379, 10.1097/01.mco.0000232896.66791.62

Hanahan, 2012, Accessories to the crime: functions of cells recruited to the tumor microenvironment, Cancer Cell, 21, 309, 10.1016/j.ccr.2012.02.022

Hannun, 2008, Principles of bioactive lipid signalling: lessons from sphingolipids, Nat. Rev. Mol. Cell Biol., 9, 139, 10.1038/nrm2329

Hardie, 2007, AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy, Nat. Rev. Mol. Cell Biol., 8, 774, 10.1038/nrm2249

Harjes, 2012, Endothelial cell metabolism and implications for cancer therapy, Br. J. Cancer, 107, 1207, 10.1038/bjc.2012.398

Hatzivassiliou, 2005, ATP citrate lyase inhibition can suppress tumor cell growth, Cancer Cell, 8, 311, 10.1016/j.ccr.2005.09.008

Hess, 2010, Inhibition of stearoylCoA desaturase activity blocks cell cycle progression and induces programmed cell death in lung cancer cells, PLoS ONE, 5, e11394, 10.1371/journal.pone.0011394

Heusinkveld, 2011, M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells, J. Immunol., 187, 1157, 10.4049/jimmunol.1100889

Higgins, 2009, Hypoxia and the metabolic phenotype of prostate cancer cells, Biochim. Biophys. Acta, 1787, 1433, 10.1016/j.bbabio.2009.06.003

Hilvo, 2011, Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression, Cancer Res., 71, 3236, 10.1158/0008-5472.CAN-10-3894

Huang, 2010, Androgen receptor survival signaling is blocked by anti-beta2-microglobulin monoclonal antibody via a MAPK/lipogenic pathway in human prostate cancer cells, J. Biol. Chem., 285, 7947, 10.1074/jbc.M109.092759

Huang, 2012, Activation of androgen receptor, lipogenesis, and oxidative stress converged by SREBP-1 is responsible for regulating growth and progression of prostate cancer cells, Mol. Cancer Res., 10, 133, 10.1158/1541-7786.MCR-11-0206

Hughes, 2005, SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast, Cell, 120, 831, 10.1016/j.cell.2005.01.012

Igal, 2010, Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer, Carcinogenesis, 31, 1509, 10.1093/carcin/bgq131

Im, 2011, Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a, Cell Metab., 13, 540, 10.1016/j.cmet.2011.04.001

Jerby, 2012, Metabolic associations of reduced proliferation and oxidative stress in advanced breast cancer, Cancer Res., 72, 5712, 10.1158/0008-5472.CAN-12-2215

Jiang, 2013, SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine, Nature, 496, 110, 10.1038/nature12038

Joyce, 2009, Microenvironmental regulation of metastasis, Nat. Rev. Cancer, 9, 239, 10.1038/nrc2618

Kaelin, 2008, Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway, Mol. Cell, 30, 393, 10.1016/j.molcel.2008.04.009

Kamphorst, 2013, Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids, Proc. Natl. Acad. Sci. USA, 110, 8882, 10.1073/pnas.1307237110

Karnezis, 2012, VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium, Cancer Cell, 21, 181, 10.1016/j.ccr.2011.12.026

Klopp, 2012, Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors, Clin. Cancer Res., 18, 771, 10.1158/1078-0432.CCR-11-1916

Kornberg, 2011, Barcoding Hedgehog for intracellular transport, Sci. Signal., 4, pe44, 10.1126/scisignal.2002447

Krishnan, 2009, Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy, Cell Metab., 9, 512, 10.1016/j.cmet.2009.05.005

Krysan, 2005, Prostaglandin E2 activates mitogen-activated protein kinase/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an epidermal growth factor receptor-independent manner, Cancer Res., 65, 6275, 10.1158/0008-5472.CAN-05-0216

Kuhajda, 1994, Fatty acid synthesis: a potential selective target for antineoplastic therapy, Proc. Natl. Acad. Sci. USA, 91, 6379, 10.1073/pnas.91.14.6379

Kuhajda, 2000, Synthesis and antitumor activity of an inhibitor of fatty acid synthase, Proc. Natl. Acad. Sci. USA, 97, 3450, 10.1073/pnas.97.7.3450

Levental, 2010, Greasing their way: lipid modifications determine protein association with membrane rafts, Biochemistry, 49, 6305, 10.1021/bi100882y

Li, 1997, PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer, Science, 275, 1943, 10.1126/science.275.5308.1943

Li, 2001, Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53, Cancer Res., 61, 1493

Li, 2006, Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha, Physiol. Genomics, 25, 450, 10.1152/physiolgenomics.00293.2005

Li, 2011, AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice, Cell Metab., 13, 376, 10.1016/j.cmet.2011.03.009

Liu, 2009, Cell and molecular mechanisms of insulin-induced angiogenesis, J. Cell. Mol. Med., 13, 4492, 10.1111/j.1582-4934.2008.00555.x

Manabe, 2003, Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions, J. Pathol., 201, 221, 10.1002/path.1430

Mason, 2012, SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids, PLoS ONE, 7, e33823, 10.1371/journal.pone.0033823

Medes, 1953, Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro, Cancer Res., 13, 27

Menendez, 2007, Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Nat. Rev. Cancer, 7, 763, 10.1038/nrc2222

Metallo, 2012, Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia, Nature, 481, 380, 10.1038/nature10602

Migita, 2008, ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer, Cancer Res., 68, 8547, 10.1158/0008-5472.CAN-08-1235

Mills, 2003, The emerging role of lysophosphatidic acid in cancer, Nat. Rev. Cancer, 3, 582, 10.1038/nrc1143

Minville-Walz, 2010, Inhibition of stearoyl-CoA desaturase 1 expression induces CHOP-dependent cell death in human cancer cells, PLoS ONE, 5, e14363, 10.1371/journal.pone.0014363

Morad, 2013, Ceramide-orchestrated signalling in cancer cells, Nat. Rev. Cancer, 13, 51, 10.1038/nrc3398

Mullen, 2012, Reductive carboxylation supports growth in tumour cells with defective mitochondria, Nature, 481, 385, 10.1038/nature10642

Nagahashi, 2012, Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis, Cancer Res., 72, 726, 10.1158/0008-5472.CAN-11-2167

Nieman, 2011, Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth, Nat. Med., 17, 1498, 10.1038/nm.2492

Nohturfft, 2009, Coordination of lipid metabolism in membrane biogenesis, Annu. Rev. Cell. Dev. Biol., 25, 539, 10.1146/annurev.cellbio.24.110707.175344

Nomura, 2010, Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis, Cell, 140, 49, 10.1016/j.cell.2009.11.027

Orita, 2008, Inhibiting fatty acid synthase for chemoprevention of chemically induced lung tumors, Clin. Cancer Res., 14, 2458, 10.1158/1078-0432.CCR-07-4177

Park, 2012, Phospholipase signalling networks in cancer, Nat. Rev. Cancer, 12, 782, 10.1038/nrc3379

Paulick, 2008, The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins, Biochemistry, 47, 6991, 10.1021/bi8006324

Pearce, 1998, The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076, Biochem. J., 334, 113, 10.1042/bj3340113

Poitout, 2008, Glucolipotoxicity: fuel excess and beta-cell dysfunction, Endocr. Rev., 29, 351, 10.1210/er.2007-0023

Porstmann, 2005, PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP, Oncogene, 24, 6465, 10.1038/sj.onc.1208802

Porstmann, 2008, SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth, Cell Metab., 8, 224, 10.1016/j.cmet.2008.07.007

Puig, 2009, Novel inhibitors of fatty acid synthase with anticancer activity, Clin. Cancer Res., 15, 7608, 10.1158/1078-0432.CCR-09-0856

Rankin, 2009, Hypoxia-inducible factor 2 regulates hepatic lipid metabolism, Mol. Cell. Biol., 29, 4527, 10.1128/MCB.00200-09

Resh, 2013, Covalent lipid modifications of proteins, Curr. Biol., 23, R431, 10.1016/j.cub.2013.04.024

Rolin, 2011, Effects of lysophospholipids on tumor microenvironment, Cancer Microenviron., 4, 393, 10.1007/s12307-011-0088-1

Roongta, 2011, Cancer cell dependence on unsaturated fatty acids implicates stearoyl-CoA desaturase as a target for cancer therapy, Mol. Cancer Res., 9, 1551, 10.1158/1541-7786.MCR-11-0126

Rysman, 2010, De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation, Cancer Res., 70, 8117, 10.1158/0008-5472.CAN-09-3871

Santolla, 2012, G protein-coupled estrogen receptor mediates the up-regulation of fatty acid synthase induced by 17β-estradiol in cancer cells and cancer-associated fibroblasts, J. Biol. Chem., 287, 43234, 10.1074/jbc.M112.417303

Santos, 2012, Lipid metabolism in cancer, FEBS J., 279, 2610, 10.1111/j.1742-4658.2012.08644.x

Scaglia, 2009, Inhibition of stearoylCoA desaturase-1 inactivates acetyl-CoA carboxylase and impairs proliferation in cancer cells: role of AMPK, PLoS ONE, 4, e6812, 10.1371/journal.pone.0006812

Seguin, 2012, The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas, Br. J. Cancer, 107, 977, 10.1038/bjc.2012.355

Seo, 2011, Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy, Cell Metab., 13, 367, 10.1016/j.cmet.2011.03.005

Shamma, 2009, Rb Regulates DNA damage response and cellular senescence through E2F-dependent suppression of N-ras isoprenylation, Cancer Cell, 15, 255, 10.1016/j.ccr.2009.03.001

Shao, 2012, Expanding roles for SREBP in metabolism, Cell Metab., 16, 414, 10.1016/j.cmet.2012.09.002

Simons, 2010, Revitalizing membrane rafts: new tools and insights, Nat. Rev. Mol. Cell Biol., 11, 688, 10.1038/nrm2977

Singh, 2009, Autophagy regulates lipid metabolism, Nature, 458, 1131, 10.1038/nature07976

Srivastava, 2010, In vitro, high-resolution 1H and 31P NMR based analysis of the lipid components in the tissue, serum, and CSF of the patients with primary brain tumors: one possible diagnostic view, NMR Biomed., 23, 113, 10.1002/nbm.1427

Steck, 1997, Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers, Nat. Genet., 15, 356, 10.1038/ng0497-356

Swinnen, 2006, Increased lipogenesis in cancer cells: new players, novel targets, Curr. Opin. Clin. Nutr. Metab. Care, 9, 358, 10.1097/01.mco.0000232894.28674.30

Tokuda, 2003, Prostate cancer cell growth is modulated by adipocyte-cancer cell interaction, BJU Int., 91, 716, 10.1046/j.1464-410X.2003.04218.x

Tokumura, 2002, Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase, J. Biol. Chem., 277, 39436, 10.1074/jbc.M205623200

Vanhaesebroeck, 2001, Synthesis and function of 3-phosphorylated inositol lipids, Annu. Rev. Biochem., 70, 535, 10.1146/annurev.biochem.70.1.535

Walker, 2011, A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans, Cell, 147, 840, 10.1016/j.cell.2011.09.045

Wang, 2010, Eicosanoids and cancer, Nat. Rev. Cancer, 10, 181, 10.1038/nrc2809

Wellen, 2009, ATP–citrate lyase links cellular metabolism to histone acetylation, Science, 324, 1076, 10.1126/science.1164097

White, 2012, Deconvoluting the context-dependent role for autophagy in cancer, Nat. Rev. Cancer, 12, 401, 10.1038/nrc3262

Willemarck, 2010, Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development, Cancer Res., 70, 9453, 10.1158/0008-5472.CAN-10-2324

Wise, 2011, Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability, Proc. Natl. Acad. Sci. USA, 108, 19611, 10.1073/pnas.1117773108

Wymann, 2008, Lipid signalling in disease, Nat. Rev. Mol. Cell Biol., 9, 162, 10.1038/nrm2335

Yao, 2006, Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis, J. Leukoc. Biol., 80, 608, 10.1189/jlb.0304175

Zaidi, 2012, ATP-citrate lyase: a key player in cancer metabolism, Cancer Res., 72, 3709, 10.1158/0008-5472.CAN-11-4112

Zaugg, 2011, Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress, Genes Dev., 25, 1041, 10.1101/gad.1987211

Zhan, 2008, Control of cell growth and survival by enzymes of the fatty acid synthesis pathway in HCT-116 colon cancer cells, Clin. Cancer Res., 14, 5735, 10.1158/1078-0432.CCR-07-5074

Zhang, 2013, 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., 104, 416, 10.1111/cas.12108

Zhou, 2004, Vascular endothelial growth factor activation of sterol regulatory element binding protein: a potential role in angiogenesis, Circ. Res., 95, 471, 10.1161/01.RES.0000139956.42923.4A

Zhu, 2012, Application of metabolic PET imaging in radiation oncology, Radiat. Res., 177, 436, 10.1667/RR2702.1