Omega-3 fatty acids in cancer prevention and control: A membrane perspective

Obesity, Inflammation and Cancer

Volumn , Issue , 2013, Pages 306-339

  Turk, Harmony F ^a   Monk, Jennifer M ^a   Hou, Tim Y ^a   Chapkin, Robert S ^a  

^a TEXAS A AND M UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84898451477     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-6819-6_12     Document Type: Chapter

References (259)

1. Sargent JR (1997) Fish oils and human diet. Br J Nutr 78(suppl 1):S5-S13
2. Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr (2001) Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res 42:1257-1265
3. Berquin IM, Edwards IJ, Chen YQ (2008) Multi-targeted therapy of cancer by omega-3 fatty acids. Cancer Lett 269:363-377
4. Caygill CP, Charlett A, Hill MJ (1996) Fat, fish, fish oil and cancer. Br J Cancer 74:159-164
5. Gerber M (2012) Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr 107(suppl 2):S228-S239
6. Pauwels EK, Kairemo K (2008) Fatty acid facts, part II: role in the prevention of carcinogenesis, or, more fish on the dish? Drug News Perspect 21:504-510
7. Gerber M (2009) Background review paper on total fat, fatty acid intake and cancers. Ann Nutr Metab 55:140-161
8. Kim S, Sandler DP, Galanko J, Martin C, Sandler RS (2010) Intake of polyunsaturated fatty acids and distal large bowel cancer risk in whites and African Americans. Am J Epidemiol 171:969-979
9. Kimura Y, Kono S, Toyomura K, Nagano J, Mizoue T, Moore MA, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N (2007) Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study. Cancer Sci 98:590-597
10. Murff HJ, Shrubsole MJ, Cai Q, Smalley WE, Dai Q, Milne GL, Ness RM, Zheng W (2012) Dietary intake of PUFA and colorectal polyp risk. Am J Clin Nutr 95:703-712
11. Sasazuki S, Inoue M, Iwasaki M, Sawada N, Shimazu T, Yamaji T, Takachi R, Tsugane S (2011) Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center-based prospective study. Int J Cancer 129:1718-1729
12. Theodoratou E, McNeill G, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, Porteous M, Dunlop M, Campbell H (2007) Dietary fatty acids and colorectal cancer: a case-control study. Am J Epidemiol 166:181-195
13. Hall MN, Chavarro JE, Lee IM, Willett WC, Ma J (2008) A 22-year prospective study of fish, n-3 fatty acid intake, and colorectal cancer risk in men. Cancer Epidemiol Biomarkers Prev 17:1136-1143
14. Geelen A, Schouten JM, Kamphuis C, Stam BE, Burema J, Renkema JM, Bakker EJ, van't Veer P, Kampman E (2007) Fish consumption, n-3 fatty acids, and colorectal cancer: a metaanalysis of prospective cohort studies. Am J Epidemiol 166:1116-1125
15. Hall MN, Campos H, Li H, Sesso HD, Stampfer MJ, Willett WC, Ma J (2007) Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 16:314-321
16. Kojima M, Wakai K, Tokudome S, Suzuki K, Tamakoshi K, Watanabe Y, Kawado M, Hashimoto S, Hayakawa N, Ozasa K, Toyoshima H, Suzuki S, Ito Y, Tamakoshi A, J.S. Group (2005) Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a prospective study. Am J Epidemiol 161:462-471
17. Pot GK, Geelen A, van Heijningen EM, Siezen CL, van Kranen HJ, Kampman E (2008) Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: an endoscopy-based case-control study. Int J Cancer 123:1974-1977
18. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69-90
19. Anti M, Marra G, Armelao F, Bartoli GM, Ficarelli R, Percesepe A, De Vitis I, Maria G, Sofo L, Rapaccini GL et al (1992) Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Gastroenterology 103:883-891
20. Bartram HP, Gostner A, Scheppach W, Reddy BS, Rao CV, Dusel G, Richter F, Richter A, Kasper H (1993) Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology 105:1317-1322
21. Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P, Parrella P, Canetta C, Gentiloni N, De Vitis I et al (1994) Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107:1709-1718
22. Courtney ED, Matthews S, Finlayson C, Di Pierro D, Belluzzi A, Roda E, Kang JY, Leicester RJ (2007) Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis 22:765-776
23. West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA (2010) Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59:918-925
24. Stern MC, Butler LM, Corral R, Joshi AD, Yuan JM, Koh WP, Yu MC (2009) Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study. J Nutrigenet Nutrigenomics 2:273-279
25. Hashimoto M, Hossain S, Yamasaki H, Yazawa K, Masumura S (1999) Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids 34:1297-1304
26. Stillwell W, Wassall SR (2003) Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 126:1-27
27. Wassall SR, Brzustowicz MR, Shaikh SR, Cherezov V, Caffrey M, Stillwell W (2004) Order from disorder, corralling cholesterol with chaotic lipids. The role of polyunsaturated lipids in membrane raft formation. Chem Phys Lipids 132:79-88
28. Chapkin RS, Wang N, Fan YY, Lupton JR, Prior IA (2008) Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta 1778:466-471
29. Kim W, Fan YY, Barhoumi R, Smith R, McMurray DN, Chapkin RS (2008) n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation. J Immunol 181:6236-6243
30. Rockett BD, Teague H, Harris M, Melton M, Williams J, Wassall SR, Shaikh SR (2012) Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function. J Lipid Res 53:674-685
31. Shaikh SR, Locascio DS, Soni SP, Wassall SR, Stillwell W (2009) Oleic-and docosahexaenoic acid-containing phosphatidylethanolamines differentially phase separate from sphingomyelin. Biochim Biophys Acta 1788:2421-2426
32. Pike LJ (2006) Rafts defined: a report on the keystone symposium on lipid rafts and cell function. J Lipid Res 47:1597-1598
33. Pike LJ (2005) Growth factor receptors, lipid rafts and caveolae: an evolving story. Biochim Biophys Acta 1746:260-273
34. Brown DA, London E (2000) Structure and function of sphingolipid-and cholesterol-rich membrane rafts. J Biol Chem 275:17221-17224
35. Simons K, Sampaio JL (2011) Membrane organization and lipid rafts. Cold Spring Harb Perspect Biol 3:a004697
36. Jacobson K, Mouritsen OG, Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 9:7-14
37. Pike LJ (2004) Lipid rafts: heterogeneity on the high seas. Biochem J 378:281-292
38. Deans JP, Robbins SM, Polyak MJ, Savage JA (1998) Rapid redistribution of CD20 to a low density detergent-insoluble membrane compartment. J Biol Chem 273:344-348
39. Field KA, Holowka D, Baird B (1997) Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 272:4276-4280
40. Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31-39
41. Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE, Okamoto T, Lisanti MP (1999) Caveolins, liquid-ordered domains, and signal transduction. Mol Cell Biol 19:7289-7304
42. Staubach S, Hanisch FG (2011) Lipid rafts: signaling and sorting platforms of cells and their roles in cancer. Expert Rev Proteomics 8:263-277
43. Hofman EG, Ruonala MO, Bader AN, Van Den Heuvel D, Voortman J, Roovers RC, Verkleij AJ, Gerritsen HC, van Bergen En Henegouwen PM (2008) EGF induces coalescence of different lipid rafts. J Cell Sci 121:2519-2528
44. Kono H, Suzuki T, Yamamoto K, Okada M, Yamamoto T, Honda Z (2002) Spatial raft coalescence represents an initial step in Fc gamma R signaling. J Immunol 169:193-203
45. Patel HH, Murray F, Insel PA (2008) G-protein-coupled receptor-signaling components in membrane raft and caveolae microdomains. Handb Exp Pharmacol 186:167-184
46. Pike LJ, Han X, Gross RW (2005) Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: a shotgun lipidomics study. J Biol Chem 280:26796-26804
47. Prior IA, Muncke C, Parton RG, Hancock JF (2003) Direct visualization of Ras proteins in spatially distinct cell surface microdomains. J Cell Biol 160:165-170
48. George KS, Wu S (2012) Lipid raft: a floating island of death or survival. Toxicol Appl Pharmacol 259:311-319
49. Alonso MA, Millan J (2001) The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci 114:3957-3965
50. Drbal K, Moertelmaier M, Holzhauser C, Muhammad A, Fuertbauer E, Howorka S, Hinterberger M, Stockinger H, Schutz GJ (2007) Single-molecule microscopy reveals heterogeneous dynamics of lipid raft components upon TCR engagement. Int Immunol 19:675-684
51. Algeciras-Schimnich A, Shen L, Barnhart BC, Murmann AE, Burkhardt JK, Peter ME (2002) Molecular ordering of the initial signaling events of CD95. Mol Cell Biol 22:207-220
52. Bang B, Gniadecki R, Gajkowska B (2005) Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes. Exp Dermatol 14:266-272
53. Hazarika P, McCarty MF, Prieto VG, George S, Babu D, Koul D, Bar-Eli M, Duvic M (2004) Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Cancer Res 64:7361-7369
54. Li YC, Park MJ, Ye SK, Kim CW, Kim YN (2006) Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am J Pathol 168:1107-1118; quiz 1404-1405
55. Patra SK (2008) Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta 1785:182-206
56. Fedida-Metula S, Feldman B, Koshelev V, Levin-Gromiko U, Voronov E, Fishman D (2012) Lipid rafts couple store-operated Ca2+ entry to constitutive activation of PKB/Akt in a Ca2+/ calmodulin-, Src-and PP2A-mediated pathway and promote melanoma tumor growth. Carcinogenesis 33:740-750
57. Irwin ME, Bohin N, Boerner JL (2011) Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biol Ther 12:718-726
58. Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM, Soudja SM, Lenne PF, Rigneault H, Olive D, Bismuth G, Nunes JA, Payrastre B, Marguet D, He HT (2008) Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol 4:538-547
59. Orr G, Hu D, Ozcelik S, Opresko LK, Wiley HS, Colson SD (2005) Cholesterol dictates the freedom of EGF receptors and HER2 in the plane of the membrane. Biophys J 89:1362-1373
60. Ringerike T, Blystad FD, Levy FO, Madshus IH, Stang E (2002) Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae. J Cell Sci 115:1331-1340
61. Roy UK, Rial NS, Kachel KL, Gerner EW (2008) Activated K-RAS increases polyamine uptake in human colon cancer cells through modulation of caveolar endocytosis. Mol Carcinog 47:538-553
62. Irwin ME, Mueller KL, Bohin N, Ge Y, Boerner JL (2011) Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol 226(9):2316-2328
63. Lacour S, Hammann A, Grazide S, Lagadic-Gossmann D, Athias A, Sergent O, Laurent G, Gambert P, Solary E, Dimanche-Boitrel MT (2004) Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res 64:3593-3598
64. Rebillard A, Tekpli X, Meurette O, Sergent O, LeMoigne-Muller G, Vernhet L, Gorria M, Chevanne M, Christmann M, Kaina B, Counillon L, Gulbins E, Lagadic-Gossmann D, Dimanche-Boitrel MT (2007) Cisplatin-induced apoptosis involves membrane fluidification via inhibition of NHE1 in human colon cancer cells. Cancer Res 67:7865-7874
65. Adachi S, Nagao T, Ingolfsson HI, Maxfield FR, Andersen OS, Kopelovich L, Weinstein IB (2007) The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res 67:6493-6501
66. Bacso Z, Bene L, Damjanovich L, Damjanovich S (2002) INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells. Biochem Biophys Res Commun 290:635-640
67. Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140:1807-1816
68. Nicolau DV Jr, Burrage K, Parton RG, Hancock JF (2006) Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane. Mol Cell Biol 26:313-323
69. Corsetto PA, Cremona A, Montorfano G, Jovenitti IE, Orsini F, Arosio P, Rizzo AM (2012) Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys 64(1):45-59
70. Ma DW, Seo J, Davidson LA, Callaway ES, Fan YY, Lupton JR, Chapkin RS (2004) n-3 PUFA alter caveolae lipid composition and resident protein localization in mouse colon. FASEB J 18:1040-1042
71. Schley PD, Brindley DN, Field CJ (2007) (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 137:548-553
72. Ye S, Tan L, Ma J, Shi Q, Li J (2010) Polyunsaturated docosahexaenoic acid suppresses oxidative stress induced endothelial cell calcium influx by altering lipid composition in membrane caveolar rafts. Prostaglandins Leukot Essent Fatty Acids 83:37-43
73. Poulogiannis G, Luo F, Arends MJ (2012) RAS signalling in the colorectum in health and disease. Cell Commun Adhes 19:1-9
74. Seo J, Barhoumi R, Johnson AE, Lupton JR, Chapkin RS (2006) Docosahexaenoic acid selectively inhibits plasma membrane targeting of lipidated proteins. FASEB J 20:770-772
75. Rogers KR, Kikawa KD, Mouradian M, Hernandez K, McKinnon KM, Ahwah SM, Pardini RS (2010) Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. Carcinogenesis 31:1523-1530
76. Turk HF, Barhoumi R, Chapkin RS (2012) Alteration of EGFR spatiotemporal dynamics suppresses signal transduction. PLoS One 7:e39682
77. Duraisamy Y, Lambert D, O'Neill CA, Padfield PJ (2007) Differential incorporation of docosahexaenoic acid into distinct cholesterol-rich membrane raft domains. Biochem Biophys Res Commun 360:885-890
78. Collett ED, Davidson LA, Fan YY, Lupton JR, Chapkin RS (2001) n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. Am J Physiol Cell Physiol 280:C1066-C1075
79. Eisenberg S, Beckett AJ, Prior IA, Dekker FJ, Hedberg C, Waldmann H, Ehrlich M, Henis YI (2011) Raft protein clustering alters N-Ras membrane interactions and activation pattern. Mol Cell Biol 31:3938-3952
80. Eisenberg S, Henis YI (2008) Interactions of Ras proteins with the plasma membrane and their roles in signaling. Cell Signal 20:31-39
81. Prior IA, Hancock JF (2012) Ras trafficking, localization and compartmentalized signalling. Semin Cell Dev Biol 23(2):145-153
82. Sehgal PB, Guo GG, Shah M, Kumar V, Patel K (2002) Cytokine signaling: STATS in plasma membrane rafts. J Biol Chem 277:12067-12074
83. Monk JM, Kim W, Callaway E, Turk HF, Foreman JE, Peters JM, He W, Weeks B, Alaniz RC, McMurray DN, Chapkin RS (2012) Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARdelta in inflammation-induced colon carcinogenesis. Am J Physiol Gastrointest Liver Physiol 302:G153-G167
84. Ravacci GR, Brentani MM, Tortelli T Jr, Torrinhas RS, Saldanha T, Torres EA, Waitzberg DL (2012) Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression. J Nutr Biochem 24:505-515
85. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436-444
86. Chen R, Rabinovitch PS, Crispin DA, Emond MJ, Bronner MP, Brentnall TA (2005) The initiation of colon cancer in a chronic inflammatory setting. Carcinogenesis 26:1513-1519
87. Ohshima H, Tazawa H, Sylla BS, Sawa T (2005) Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res 591:110-122
88. Shishodia S, Aggarwal BB (2004) Nuclear factor-kappaB: a friend or a foe in cancer? Biochem Pharmacol 68:1071-1080
89. Yan SR, Joseph RR, Rosen K, Reginato MJ, Jackson A, Allaire N, Brugge JS, Jobin C, Stadnyk AW (2005) Activation of NF-kappaB following detachment delays apoptosis in intestinal epithelial cells. Oncogene 24:6482-6491
90. Janakiram NB, Mohammed A, Rao CV (2011) Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer. Cancer Metastasis Rev 30:507-523
91. Tenesa A, Dunlop MG (2009) New insights into the aetiology of colorectal cancer from genome-wide association studies. Nat Rev Genet 10:353-358
92. Rustgi AK (2007) The genetics of hereditary colon cancer. Genes Dev 21:2525-2538
93. Chapkin RS, McMurray DN, Lupton JR (2007) Colon cancer, fatty acids and antiinfl ammatory compounds. Curr Opin Gastroenterol 23:48-54
94. Feagins LA, Souza RF, Spechler SJ (2009) Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer. Nat Rev Gastroenterol Hepatol 6:297-305
95. Lakatos PL, Lakatos L (2008) Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J Gastroenterol 14:3937-3947
96. Choi J, Yoon SH, Kim JE, Rhee KH, Youn HS, Chung MH (2002) Gene-specific oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa. Int J Cancer 99:485-490
97. Kraus S, Arber N (2009) Inflammation and colorectal cancer. Curr Opin Pharmacol 9:405-410
98. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST (2003) Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci USA 100:1751-1756
99. Dooper MM, Wassink L, M'Rabet L, Graus YM (2002) The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype. Immunology 107:152-159
100. Miles EA, Allen E, Calder PC (2002) In vitro effects of eicosanoids derived from different 20-carbon fatty acids on production of monocyte-derived cytokines in human whole blood cultures. Cytokine 20:215-223
101. Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Ferretti A, Erickson KL, Yu R, Chandra RK, Mackey BE (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34:317-324
102. Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121:547-555
103. Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, Calder PC (2006) Doserelated effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83:331-342
104. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC (2003) Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Am J Clin Nutr 78:376-382
105. von Schacky C, Kiefl R, Jendraschak E, Kaminski WE (1993) n-3 fatty acids and cysteinylleukotriene formation in humans in vitro, ex vivo, and in vivo. J Lab Clin Med 121:302-309
106. Maitra A, Ashfaq R, Gunn CR, Rahman A, Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Wilentz RE (2002) Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol 118:194-201
107. Rao CV, Reddy BS (2004) NSAIDs and chemoprevention. Curr Cancer Drug Targets 4:29-42
108. Buchanan FG, DuBois RN (2006) Connecting COX-2 and Wnt in cancer. Cancer Cell 9:6-8
109. Greenhough A, Wallam CA, Hicks DJ, Moorghen M, Williams AC, Paraskeva C (2010) The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene 29:3398-3410
110. Park SW, Kim HS, Choi MS, Jeong WJ, Heo DS, Kim KH, Sung MW (2011) The effects of the stromal cell-derived cyclooxygenase-2 metabolite prostaglandin E2 on the proliferation of colon cancer cells. J Pharmacol Exp Ther 336:516-523
111. Wang D, Dubois RN (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29:781-788
112. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN (1994) Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107:1183-1188
113. Kulkarni N, Zang E, Kelloff G, Reddy BS (1992) Effect of the chemopreventive agents piroxicam and D, L-alpha-difluoromethylornithine on intermediate biomarkers of colon carcinogenesis. Carcinogenesis 13:995-1000
114. Fan YY, Monk JM, Hou TY, Callway E, Vincent L, Weeks B, Yang P, Chapkin RS (2012) Characterization of an arachidonic acid-deficient (Fads1 knockout) mouse model. J Lipid Res 53:1287-1295
115. Badawi AF, El-Sohemy A, Stephen LL, Ghoshal AK, Archer MC (1998) The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands. Carcinogenesis 19:905-910
116. Hamid R, Singh J, Reddy BS, Cohen LA (1999) Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors. Int J Oncol 14:523-528
117. Ringbom T, Huss U, Stenholm A, Flock S, Skattebol L, Perera P, Bohlin L (2001) Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod 64:745-749
118. Singh J, Hamid R, Reddy BS (1997) Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res 57:3465-3470
119. Gravaghi C, La Perle KM, Ogrodwski P, Kang JX, Quimby F, Lipkin M, Lamprecht SA (2011) Cox-2 expression, PGE(2) and cytokines production are inhibited by endogenously synthesized n-3 PUFA in inflamed colon of fat-1 mice. J Nutr Biochem 22:360-365
120. Calviello G, Di Nicuolo F, Gragnoli S, Piccioni E, Serini S, Maggiano N, Tringali G, Navarra P, Ranelletti FO, Palozza P (2004) n-3 PUFA reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway. Carcinogenesis 25:2303-2310
121. Habbel P, Weylandt KH, Lichopoj K, Nowak J, Purschke M, Wang JD, He CW, Baumgart DC, Kang JX (2009) Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells. World J Gastroenterol 15:1079-1084
122. Swamy MV, Cooma I, Patlolla JM, Simi B, Reddy BS, Rao CV (2004) Modulation of cyclooxygenase-2 activities by the combined action of celecoxib and decosahexaenoic acid: novel strategies for colon cancer prevention and treatment. Mol Cancer Ther 3:215-221
123. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278:14677-14687
124. Serhan CN, Chiang N, Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8:349-361
125. Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192:1197-1204
126. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG (2004) Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 101:8491-8496
127. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196:1025-1037
128. Bannenberg G, Arita M, Serhan CN (2007) Endogenous receptor agonists: resolving inflammation. ScientificWorldJournal 7:1440-1462
129. Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201:713-722
130. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345-4355
131. Darnell JE Jr (2002) Transcription factors as targets for cancer therapy. Nat Rev Cancer 2:740-749
132. Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749-759
133. Kojima M, Morisaki T, Sasaki N, Nakano K, Mibu R, Tanaka M, Katano M (2004) Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. Anti-cancer Res 24:675-681
134. Meylan E, Dooley AL, Feldser DM, Shen L, Turk E, Ouyang C, Jacks T (2009) Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma. Nature 462:104-107
135. Naugler WE, Karin M (2008) NF-kappaB and cancer-identifying targets and mechanisms. Curr Opin Genet Dev 18:19-26
136. Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441:431-436
137. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285-296
138. Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68:323-328
139. Becker C, Fantini MC, Schramm C, Lehr HA, Wirtz S, Nikolaev A, Burg J, Strand S, Kiesslich R, Huber S, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Galle PR, Blessing M, Rose-John S, Neurath MF (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:491-501
140. Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276:16683-16689
141. Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ (2003) NF-kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284:L84-L89
142. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM (2007) Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18:250-258
143. Zhao Y, Joshi-Barve S, Barve S, Chen LH (2004) Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 23:71-78
144. Nowak J, Weylandt KH, Habbel P, Wang J, Dignass A, Glickman JN, Kang JX (2007) Colitisassociated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis 28:1991-1995
145. Hudert CA, Weylandt KH, Lu Y, Wang J, Hong S, Dignass A, Serhan CN, Kang JX (2006) Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci USA 103:11276-11281
146. Fan YY, Ly LH, Barhoumi R, McMurray DN, Chapkin RS (2004) Dietary docosahexaenoic acid suppresses T cell protein kinase C theta lipid raft recruitment and IL-2 production. J Immunol 173:6151-6160
147. Maziere C, Conte MA, Degonville J, Ali D, Maziere JC (1999) Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NFkappaB. Biochem Biophys Res Commun 265:116-122
148. Gee JM, Robertson JF, Ellis IO, Nicholson RI (2000) Impact of activation of MAP kinase family members on endocrine response and survival in clinical breast cancer. Eur J Cancer 36(suppl 4):105
149. Neyns B, Teugels E, Bourgain C, Birrerand M, De Greve J (1999) Alteration of jun protooncogene status by plasmid transfection affects growth of human ovarian cancer cells. Int J Cancer 82:687-693
150. Prusty BK, Das BC (2005) Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin. Int J Cancer 113:951-960
151. Wang H, Birkenbach M, Hart J (2000) Expression of Jun family members in human colorectal adenocarcinoma. Carcinogenesis 21:1313-1317
152. Ashida R, Tominaga K, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Mitsuyama S, Iwao H, Arakawa T (2005) AP-1 and colorectal cancer. Inflammopharmacology 13:113-125
153. Eferl R, Wagner EF (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3:859-868
154. Jia Q, Ivanov I, Zlatev ZZ, Alaniz RC, Weeks BR, Callaway ES, Goldsby JS, Davidson LA, Fan YY, Zhou L, Lupton JR, McMurray DN, Chapkin RS (2011) Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice. Br J Nutr 106:519-529
155. Devarajan E, Huang S (2009) STAT3 as a central regulator of tumor metastases. Curr Mol Med 9:626-633
156. Jarnicki A, Putoczki T, Ernst M (2010) Stat3: linking inflammation to epithelial cancer- more than a "gut" feeling? Cell Div 5:14
157. Fan YY, Spencer TE, Wang N, Moyer MP, Chapkin RS (2003) Chemopreventive n-3 fatty acids activate RXRalpha in colonocytes. Carcinogenesis 24:1541-1548
158. Jump DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277:8755-8758
159. Zand H, Rhimipour A, Bakhshayesh M, Shafiee M, Nour Mohammadi I, Salimi S (2007) Involvement of PPAR-gamma and p53 in DHA-induced apoptosis in Reh cells. Mol Cell Biochem 304:71-77
160. Carter AB, Misyak SA, Hontecillas R, Bassaganya-Riera J (2009) Dietary modulation of inflammation-induced colorectal cancer through PPARgamma. PPAR Res 2009:498352
161. Lefebvre M, Paulweber B, Fajas L, Woods J, McCrary C, Colombel JF, Najib J, Fruchart JC, Datz C, Vidal H, Desreumaux P, Auwerx J (1999) Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol 162:331-340
162. Saez E, Tontonoz P, Nelson MC, Alvarez JG, Ming UT, Baird SM, Thomazy VA, Evans RM (1998) Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat Med 4:1058-1061
163. Voutsadakis IA (2007) Peroxisome proliferator-activated receptor gamma (PPARgamma) and colorectal carcinogenesis. J Cancer Res Clin Oncol 133:917-928
164. Szanto A, Nagy L (2008) The many faces of PPARgamma: anti-inflammatory by any means? Immunobiology 213:789-803
165. Thompson EA (2007) PPARgamma physiology and pathology in gastrointestinal epithelial cells. Mol Cells 24:167-176
166. Karrasch T, Jobin C (2008) NF-kappaB and the intestine: friend or foe? Inflamm Bowel Dis 14:114-124
167. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759-763
168. Kong W, Yen JH, Vassiliou E, Adhikary S, Toscano MG, Ganea D (2010) Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family. Lipids Health Dis 9:12
169. Zapata-Gonzalez F, Rueda F, Petriz J, Domingo P, Villarroya F, Diaz-Delfin J, de Madariaga MA, Domingo JC (2008) Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison with other polyunsaturated fatty acids. J Leukoc Biol 84:1172-1182
170. Zhao P, Xia HR, Lu GW, Li LX, Meng XL (2004) [The analysis for Raman spectra of Nd:YVO4]. Guang Pu Xue Yu Guang Pu Fen Xi 24:71-73
171. Forman BM, Chen J, Evans RM (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94:4312-4317
172. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, Devchand P, Wahli W, Willson TM, Lenhard JM, Lehmann JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 94:4318-4323
173. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV (1999) Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 3:397-403
174. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM (2010) GPR120 is an omega-3 fatty acid receptor mediating potent antiinfl ammatory and insulin-sensitizing effects. Cell 142:687-698
175. Im DS (2012) Omega-3 fatty acids in anti-inflammation (pro-resolution) and GPCRs. Prog Lipid Res 51:232-237
176. Chandramouli A, Mercado-Pimentel ME, Hutchinson A, Gibadulinova A, Olson ER, Dickinson S, Shanas R, Davenport J, Owens J, Bhattacharyya AK, Regan JW, Pastorekova S, Arumugam T, Logsdon CD, Nelson MA (2010) The induction of S100p expression by the prostaglandin E(2) (PGE(2))/EP4 receptor signaling pathway in colon cancer cells. Cancer Biol Ther 10:1056-1066
177. Cherukuri DP, Chen XB, Goulet AC, Young RN, Han Y, Heimark RL, Regan JW, Meuillet E, Nelson MA (2007) The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells. Exp Cell Res 313:2969-2979
178. Hawcroft G, Loadman PM, Belluzzi A, Hull MA (2010) Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells. Neoplasia 12:618-627
179. Arita M, Ohira T, Sun YP, Elangovan S, Chiang N, Serhan CN (2007) Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J Immunol 178:3912-3917
180. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA 107:1660-1665
181. Fan YY, McMurray DN, Ly LH, Chapkin RS (2003) Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr 133:1913-1920
182. Simons K, Vaz WL (2004) Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct 33:269-295
183. Zech T, Ejsing CS, Gaus K, de Wet B, Shevchenko A, Simons K, Harder T (2009) Accumulation of raft lipids in T-cell plasma membrane domains engaged in TCR signalling. EMBO J 28:466-476
184. Rentero C, Zech T, Quinn CM, Engelhardt K, Williamson D, Grewal T, Jessup W, Harder T, Gaus K (2008) Functional implications of plasma membrane condensation for T cell activation. PLoS One 3:e2262
185. Williams JA, Batten SE, Harris M, Rockett BD, Shaikh SR, Stillwell W, Wassall SR (2012) Docosahexaenoic and eicosapentaenoic acids segregate differently between raft and nonraft domains. Biophys J 103:228-237
186. Kwiatkowska K (2010) One lipid, multiple functions: how various pools of PI(4,5)P(2) are created in the plasma membrane. Cell Mol Life Sci 67:3927-3946
187. Holub BJ, Kuksis A, Thompson W (1970) Molecular species of mono-, di-, and triphosphoinositides of bovine brain. J Lipid Res 11:558-564
188. Inoue M, Murase S, Okuyama H (1984) Acyl coenzyme a: phospholipid acyltransferases in porcine platelets discriminate between omega-3 and omega-6 unsaturated fatty acids. Arch Biochem Biophys 231:29-37
189. Hou TY, Monk JM, Fan YY, Barhoumi R, Chen YQ, Rivera GM, McMurray DN, Chapkin RS (2012) n-3 polyunsaturated fatty acids suppress phosphatidylinositol 4,5-bisphosphatedependent actin remodelling during CD4+ T-cell activation. Biochem J 443:27-37
190. Jolly CA, Jiang YH, Chapkin RS, McMurray DN (1997) Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide. J Nutr 127:37-43
191. Dustin ML, Depoil D (2011) New insights into the T cell synapse from single molecule techniques. Nat Rev Immunol 11:672-684
192. Tybulewicz VL, Henderson RB (2009) Rho family GTPases and their regulators in lymphocytes. Nat Rev Immunol 9:630-644
193. Webb Y, Hermida-Matsumoto L, Resh MD (2000) Inhibition of protein palmitoylation, raft localization, and T cell signaling by 2-bromopalmitate and polyunsaturated fatty acids. J Biol Chem 275:261-270
194. Liang X, Nazarian A, Erdjument-Bromage H, Bornmann W, Tempst P, Resh MD (2001) Heterogeneous fatty acylation of Src family kinases with polyunsaturated fatty acids regulates raft localization and signal transduction. J Biol Chem 276:30987-30994
195. Zeyda M, Staffler G, Horejsi V, Waldhausl W, Stulnig TM (2002) LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. J Biol Chem 277:28418-28423
196. Zeyda M, Szekeres AB, Saemann MD, Geyeregger R, Stockinger H, Zlabinger GJ, Waldhausl W, Stulnig TM (2003) Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in inhibition of mitogen-activated protein kinase and nuclear factor activation. J Immunol 170:6033-6039
197. Barr VA, Balagopalan L, Barda-Saad M, Polishchuk R, Boukari H, Bunnell SC, Bernot KM, Toda Y, Nossal R, Samelson LE (2006) T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway. Traffic 7:1143-1162
198. Chichili GR, Westmuckett AD, Rodgers W (2010) T cell signal regulation by the actin cytoskeleton. J Biol Chem 285:14737-14746
199. Hashimoto-Tane A, Yokosuka T, Ishihara C, Sakuma M, Kobayashi W, Saito T (2010) T-cell receptor microclusters critical for T-cell activation are formed independently of lipid raft clustering. Mol Cell Biol 30:3421-3429
200. Eibert SM, Lee KH, Pipkorn R, Sester U, Wabnitz GH, Giese T, Meuer SC, Samstag Y (2004) Cofilin peptide homologs interfere with immunological synapse formation and T cell activation. Proc Natl Acad Sci USA 101:1957-1962
201. Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, Germain RN, Delon J (2004) ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol 5:272-279
202. Huang Y, Burkhardt JK (2007) T-cell-receptor-dependent actin regulatory mechanisms. J Cell Sci 120:723-730
203. Nolz JC, Medeiros RB, Mitchell JS, Zhu P, Freedman BD, Shimizu Y, Billadeau DD (2007) WAVE2 regulates high-affinity integrin binding by recruiting vinculin and talin to the immunological synapse. Mol Cell Biol 27:5986-6000
204. Padrick SB, Cheng HC, Ismail AM, Panchal SC, Doolittle LK, Kim S, Skehan BM, Umetani J, Brautigam CA, Leong JM, Rosen MK (2008) Hierarchical regulation of WASP/WAVE proteins. Mol Cell 32:426-438
205. Geyeregger R, Zeyda M, Zlabinger GJ, Waldhausl W, Stulnig TM (2005) Polyunsaturated fatty acids interfere with formation of the immunological synapse. J Leukoc Biol 77:680-688
206. Quann EJ, Liu X, Altan-Bonnet G, Huse M (2011) A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells. Nat Immunol 12:647-654
207. Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, Hoth M (2007) T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci USA 104:14418-14423
208. Schwindling C, Quintana A, Krause E, Hoth M (2010) Mitochondria positioning controls local calcium influx in T cells. J Immunol 184:184-190
209. Quintana A, Pasche M, Junker C, Al-Ansary D, Rieger H, Kummerow C, Nunez L, Villalobos C, Meraner P, Becherer U, Rettig J, Niemeyer BA, Hoth M (2011) Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. EMBO J 30:3895-3912
210. Muller MR, Rao A (2010) NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol 10:645-656
211. Padhan K, Varma R (2010) Immunological synapse: a multi-protein signalling cellular apparatus for controlling gene expression. Immunology 129:322-328
212. Tuosto L (2011) NF-kappaB family of transcription factors: biochemical players of CD28 co-stimulation. Immunol Lett 135:1-9
213. Waite JC, Skokos D (2012) Th17 response and inflammatory autoimmune diseases. Int J Inflam 2012:819467
214. Balkwill F, Coussens LM (2004) Cancer: an inflammatory link. Nature 431:405-406
215. Miyahara Y, Odunsi K, Chen W, Peng G, Matsuzaki J, Wang RF (2008) Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci USA 105:15505-15510
216. Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G (2010) Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 184:1630-1641
217. Kryczek I, Wei S, Zou L, Altuwaijri S, Szeliga W, Kolls J, Chang A, Zou W (2007) Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol 178:6730-6733
218. Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254-3261
219. Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, Xue X, Wei G, Liu X, Fang G (2008) The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 374:533-537
220. Kato T, Furumoto H, Ogura T, Onishi Y, Irahara M, Yamano S, Kamada M, Aono T (2001) Expression of IL-17 mRNA in ovarian cancer. Biochem Biophys Res Commun 282:735-738
221. Steiner GE, Newman ME, Paikl D, Stix U, Memaran-Dagda N, Lee C, Marberger MJ (2003) Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate. Prostate 56:171-182
222. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101:2620-2627
223. Tesmer LA, Lundy SK, Sarkar S, Fox DA (2008) Th17 cells in human disease. Immunol Rev 223:87-113
224. Maniati E, Soper R, Hagemann T (2010) Up for mischief? IL-17/Th17 in the tumour microenvironment. Oncogene 29:5653-5662
225. Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, Seikour A, Charachon A, Karoui M, Leroy K, Farcet JP, Sobhani I (2008) High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut 57:772-779
226. Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, Lin Z, Zhu B (2011) IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun 407:348-354
227. Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, Berger A, Bruneval P, Fridman WH, Pages F, Galon J (2011) Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 71:1263-1271
228. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL (2010) Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 107:5540-5544
229. Nam JS, Terabe M, Kang MJ, Chae H, Voong N, Yang YA, Laurence A, Michalowska A, Mamura M, Lonning S, Berzofsky JA, Wakefield LM (2008) Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 68:3915-3923
230. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17T cell responses. Nat Med 15:1016-1022
231. He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, Xu H (2010) IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 184:2281-2288
232. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206:1457-1464
233. Hyun YS, Han DS, Lee AR, Eun CS, Youn J, Kim HY (2012) Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 33:931-936
234. Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, Wei L, Takahashi H, Sun HW, Kanno Y, Powrie F, O'Shea JJ (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32:605-615
235. Kortylewski M, Xin H, Kujawski M, Lee H, Liu Y, Harris T, Drake C, Pardoll D, Yu H (2009) Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 15:114-123
236. Maloy KJ, Kullberg MC (2008) IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol 1:339-349
237. Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M (2006) IL-23 promotes tumour incidence and growth. Nature 442:461-465
238. Fiaschi T, Chiarugi P (2012) Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol 2012:762825
239. Babior BM (1999) NADPH oxidase: an update. Blood 93:1464-1476
240. Chiarugi P, Fiaschi T (2007) Redox signalling in anchorage-dependent cell growth. Cell Signal 19:672-682
241. Storz P (2005) Reactive oxygen species in tumor progression. Front Biosci 10:1881-1896
242. Chapkin RS, Hong MY, Fan YY, Davidson LA, Sanders LM, Henderson CE, Barhoumi R, Burghardt RC, Turner ND, Lupton JR (2002) Dietary n-3 PUFA alter colonocyte mitochondrial membrane composition and function. Lipids 37:193-199
243. Hong MY, Chapkin RS, Barhoumi R, Burghardt RC, Turner ND, Henderson CE, Sanders LM, Fan YY, Davidson LA, Murphy ME, Spinka CM, Carroll RJ, Lupton JR (2002) Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes. Carcinogenesis 23:1919-1925
244. Costantini P, Jacotot E, Decaudin D, Kroemer G (2000) Mitochondrion as a novel target of anti-cancer chemotherapy. J Natl Cancer Inst 92:1042-1053
245. Ng Y, Barhoumi R, Tjalkens RB, Fan YY, Kolar S, Wang N, Lupton JR, Chapkin RS (2005) The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis 26:1914-1921
246. Fan YY, Ran Q, Toyokuni S, Okazaki Y, Callaway ES, Lupton JR, Chapkin RS (2011) Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice. Cancer Prev Res 4:1267-1274
247. Kolar S, Barhoumi R, Jones CK, Wesley J, Lupton JR, Fan YY, Chapkin RS (2011) Interactive effects of fatty acid and butyrate-induced mitochondrial Ca(2)(+) loading and apoptosis in colonocytes. Cancer 117:5294-5303
248. Kolar SS, Barhoumi R, Callaway ES, Fan YY, Wang N, Lupton JR, Chapkin RS (2007) Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2+) accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol 293:G935-G943
249. Crim KC, Sanders LM, Hong MY, Taddeo SS, Turner ND, Chapkin RS, Lupton JR (2008) Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. Carcinogenesis 29:1415-1420
250. Sanders LM, Henderson CE, Hong MY, Barhoumi R, Burghardt RC, Wang N, Spinka CM, Carroll RJ, Turner ND, Chapkin RS, Lupton JR (2004) An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis. J Nutr 134:3233-3238
251. Saw CL, Huang Y, Kong AN (2010) Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol 79:421-430
252. Kim W, Fan YY, Smith R, Patil B, Jayaprakasha GK, McMurray DN, Chapkin RS (2009) Dietary curcumin and limonin suppress CD4+ T-cell proliferation and interleukin-2 production in mice. J Nutr 139:1042-1048
253. Simopoulos AP (1991) Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 54:438-463
254. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR (2011) Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 93:950-962
255. Russo GL (2009) Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 77:937-946
256. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365-379
257. Colditz GA, Wolin KY, Gehlert S (2012) Applying what we know to accelerate cancer prevention. Sci Transl Med 4:127rv124
258. Moses H III, Dorsey ER, Matheson DH, Thier SO (2005) Financial anatomy of biomedical research. JAMA 294:1333-1342
259. Kaiser J (2012) Profile: Bert Vogelstein. Cancer genetics with an edge. Science 337:282-284