LIPID METABOLISM DISORDERS In PANCREATIC CANCER
Abstract
In pancreatic cancer (PC) proved the role of obesity not only as a PC risk factor, but also as a factor associated with reduced survival in PC in adulthood. In PC is marked by increased lipogenesis: an increased need of cancer cells in the fatty acid (FA) is implemented not only by increasing lipogenesis de novo, but also by the exogenous FA assimilation, although several meta-analyses have not confirmed the importance of dietary fat in increasing the PC risk. Metabolic reprogramming of cancer cells is aimed at ensuring the rapid proliferation of tumor cells: the transition to aerobic glycolysis, increased expression of enzymes involved in the FA formation (citrate-synthase, ATP-citrate lyase and FA synthase - FASN), due to a mutation of the gene TP53 . As therapeutic agents in PC offer to inhibit FASN, and also impact prenylation and post-prenylation of oncogenes, in particular, KRAS , known as drugs, given the pleiotropic effect of atorvastatin and newly synthesized inhibitor farnesyltransferase R115777.
About the Authors
I. N. Grigorieva
Institute of Internal and Preventive Medicine - Branch of Federal Reseach Institute of Cytology and Genetics of SB RAS; Novosibirsk State National Research University
Russian Federation
Russian Federation
O. V. Efimova
Institute of Internal and Preventive Medicine - Branch of Federal Reseach Institute of Cytology and Genetics of SB RAS; City Clinical Hospital N 7
Russian Federation
Russian Federation
T. I. Romanova
Institute of Internal and Preventive Medicine - Branch of Federal Reseach Institute of Cytology and Genetics of SB RAS
Russian Federation
Russian Federation
References
1. Григорьева И.Н. Острый и хронический панкреатит. Новосибирск: Наука, 2011. 101 с.
2. Григорьева И.Н., Ефимова О.В. Вклад фенотипа в канцерогенез поджелудочной железы // Дневник Каз. мед. школы. 2015. № 1. C. 37-41.
3. Григорьева И.Н., Ефимова О.В., Суворова Т.С., Тов Н.Л. Панкреатит, рак поджелудочной железы и ожирение: гипотезы и факты // ЭиКГ. 2014. № 9. C. 4-10.
4. Григорьева И.Н., Ефимова О.В., Тов Н.Л., Суворова Т.С. Генетические аспекты рака поджелудочной железы // ЭиКГ. 2014. № 10. C. 70-76.
5. Swierczynski J., Hebanowska A., Sledzinski T. Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer // World J. Gastroenterol. 2014. Vol. 20, N 9. P. 2279-2303.
6. Warburg O. The metabolism of tumors. London: Constable, 1930.
7. Van der Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation // Science. 2009. Vol. 324. P. 1029-1033.
8. Куликов В.А., Беляева Л.Е. Метаболизм раковой клетки как метаболическая мишень // Вест. Витебского гос. мед. ун-та. 2016. № 6. С. 7-20.
9. Куликов В.А., Беляева Л.Е. Метаболическое перепрограммирование раковых клеток // Вест. Витебского гос. мед. ун-та. 2013. № 2. С. 6-16.
10. Зиновьева Д.А., Неелова О.В. Липиды, их биологическая роль и применение в медицине // Современные наукоемкие технологии. 2014. № 7. C. 88.
11. Hanai J., Doro N., Seth P. et al. ATP citrate lyase knockdown impacts cancer stem cells in vitro // Cell Death. Dis. 2013. N 4. e696.
12. Schlichtholz B., Turyn J., Goyke E. et al. Enhanced citrate synthase activity in human pancreatic cancer // Pancreas. 2005. Vol. 30. P. 99-104.
13. Alo P., Amini M., Piro F. et al. Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma // Anticancer Res. 2007. Vol. 27. P. 2523-2527.
14. Witkiewicz A., Nguyen K., Dasgupta A. et al. Co-expression of fatty acid synthase and caveolin-1 in pancreatic ductal adenocarcinoma: implications for tumor progression and clinical outcome // Cell Cycle. 2008. Vol. 7. P. 3021-3025.
15. Walter K., Hong S., Nyhan S. et al. Serum fatty acid synthase as a marker of pancreatic neoplasia // Cancer. Epidemiol. Biomarkers Prev. 2009. Vol. 18, N 9. P. 2380-2385.
16. Yang Y., Liu H., Li Z. et al. Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers // Int. J. Biochem. Mol. Biol. 2011. Vol. 2, N 1. P. 89-98.
17. Menendez J.A., Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis // Nature reviews. Cancer. 2007. Vol. 7, N 10. P. 763-777.
18. Nishi K. Suzuki K., Sawamoto J. Inhibition of Fatty Acid Synthesis Induces Apoptosis of Human Pancreatic Cancer Cells // Anticancer Res. 2016. Vol. 36, N 9. P. 4655-4660.
19. Ookhtens M., Kannan R., Lyon I. et al. Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor // Am. J. Physiol. 1984. Vol. 247. P. 146-153.
20. Louie S., Roberts L., Mulvihill M. et al. Cancer Cells Incorporate and Remodel Exogenous Palmitate into Structural and Oncogenic Signaling Lipids // Biochim. Biophys. Acta. 2013. Vol. 1831, N 10. P. 1566-1572.
21. Kuemmerle N.B., Rysman E., Lombardo P.S. et al. Lipoprotein lipase links dietary fat to solid tumor cell proliferation // Mol. Cancer Ther. 2011. Vol. 10. P. 427-436.
22. Zaidi N., Lupien L., Kuemmerle N. et al. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids // Prog. Lipid Res. 2013. Vol. 52. P. 585-589.
23. Tania M., Khan M.A., Song Y. Association of lipid metabolism with ovarian cancer // Curr. Oncol. 2010. Vol. 17, N 5. P. 6-11.
24. Roebuck B.D., Yager J.D., Longnecker D.S. Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat // Cancer Res. 1981. Vol. 41, N 10. P. 3961-3966.
25. Birt D., Salmasi S., Pour P.M. Enhancement of experimental pancreatic cancer in Syrian golden hamsters by dietary fat // J. Natl. Cancer Inst. 1981. Vol. 67, N 6. P. 1327-1332.
26. Stolzenberg-Solomon R.Z., Pietinen P., Taylor P.R. et al. Prospective study of diet and pancreatic cancer in male smokers // Am. J. Epidemiol. 2002. Vol. 155, N 9. P. 783.
27. Chan J.M., Wang F., Holly E.A. Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California // Cancer Causes Control. 2007. Vol. 18, N 10. P. 1153-1167.
28. Thiébaut A.C., Jiao L., Silverman D.T. et al. Dietary fatty acids and pancreatic cancer in the NIH-AARP Diet and Health Study // J. Natl. Cancer Inst. 2009. Vol. 101, N 14. P. 1001-1011.
29. Ghadirian P., Thouez J.P., PetitClerc C. International comparisons of nutrition and mortality from pancreatic cancer // Cancer Detect Prev. 1991. Vol. 15, N 5. P. 357-362.
30. Zhang J., Zhao Z., Berkel H.J. Animal fat consumption and pancreatic cancer incidence: evidence of interaction with cigarette smoking // Ann. Epidemiol. 2005. Vol. 15, N 7. P. 500-508.
31. Nöthlings U., Wilkens L., Murphy S. et al. Meat and fat intake as risk factors for pancrea-tic cancer: the multiethnic cohort study // J. Natl. Cancer Inst. 2005. Vol. 97, N 19. P. 1458.
32. Heinen M.M., Verhage B.A.J., Goldbohm R.A. et al. Meat and fat intake and pancreatic cancer risk in the Netherlands Cohort Study // Int. J. Cancer. 2009. Vol. 125, N 5. P. 1118-1126.
33. Meinhold C.L., Dodd K.W., Jiao L. et al. Available carbohydrates, glycemic load, and pancreatic cancer: Is there a link? // Am. J. Epidemiol. 2010. Vol. 171, N 11. P. 1174.
34. Shen Q.W., Yao Q.Y. Total fat consumption and pancreatic cancer risk: a meta-analysis of epidemiologic studies // Eur. J. Cancer Prev. 2015. Vol. 24, N 4. P. 278-285.
35. Lin Y., Tamakoshi A., Hayakawa T. Nutritional factors and risk of pancreatic cancer: a population-based case-control study based on direct interview in Japan // J. Gastroenterol. 2005. Vol. 40, N 3. P. 297-301.
36. Hu J., La Vecchia C., de Groh M. Dietary cholesterol intake and cancer // Ann. Oncol. 2012. Vol. 23, N 2. P. 491-500.
37. Howe G.R., Jain M., Miller A.B. Dietary factors and risk of pancreatic cancer: results of a Canadian population-based case-control study // Int. J. Cancer. 1990. Vol. 45, N 4. P. 604-608.
38. Bueno de Mesquita H., Maisonneuve P., Runia S. et al. Intake of foods and nutrients and cancer of the exocrine pancreas: a population-based case-control study in the Netherlands // Int. J. Cancer. 1991. Vol. 48, N 4. P. 540-549.
39. Lucenteforte E., Talamini R., Bosetti C. et al. Macronutrients, fatty acids, cholesterol and pancreatic cancer // Eur. J. Cancer 2010. Vol. 46, N 3. P. 581-587.
40. Chen X., Zhou T., Chen M. Meta analysis of the association of cholesterol with pancreatic carcinoma risk // J. BUON. 2015. Vol. 20, N 1. P. 109-113.
41. Wang J., Wang W.-J., Zhai L. Association of cholesterol with risk of pancreatic cancer: A meta-analysis // World J. Gastroenterol. 2015. Vol. 21, N 12. P. 3711-3719.
42. Swierczynski J., Sledzinski T. The role of adipokines and gastrointestinal tract hormones in obesity // Principles of metabolic surgery. Berlin Heidelberg: Spriger, 2012. P. 53-79.
43. Григорьева И.Н., Ефимова О.В., Рагино Ю.И., Суворова Т.С., Тов Н.Л., Романова Т.И. Показатели липидного обмена и ожирение у больных с различной патологией поджелудочной железы // РЖГГК. 2017. Т. XXVII, № 5 (прил. 49). С. 179.
44. Larsson S., Orsini N., Wolk A. Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies // Int. J. Cancer. 2007. Vol. 120, N 9. P. 1993-1998.
45. Preziosi G., Oben J., Fusai G. Obesity and pancreatic cancer // Surg. Oncol. 2014. Vol. 23, N 2. P. 61-71.
46. Yu-Qi Shi., Yang Jing., Du Peng. et al. Effect of Body Mass Index on Overall Survival of Pancreatic Cancer // Medicine (Baltimore). 2016. Vol. 95, N 14. P. e3305.
47. Luo J., Iwasaki M., Inoue M. Body mass index, physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large-scale population-based cohort study in Japan - the JPHC study // Cancer Causes Control. 2007. Vol. 18, N 6. P. 603-612.
48. Lin Y., Kikuchi S., Tamakoshi A. Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort // Int. J. Cancer 2007. Vol. 120, N 12. P. 2665-2671.
49. Wu Q., Chen G., Wu W.M. et al. Metabolic syndrome components and risk factors for pancreatic adenocarcinoma: a case-control study in China // Digestion. 2012. Vol. 86, N 4. P. 294-301.
50. Stolzenberg-Solomon R.Z., Pietinen P., Taylor P.R. et al. A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland) // Cancer Causes Control. 2002. Vol. 13, N 5. P. 417-426.
51. Романова Т.И., Григорьева И.Н., Ефимова О.В. Рак поджелудочной железы. Некоторые молекулярные и генетические механизмы онкогенеза как мишень для терапии // Эксперим. и клин. гастроэнтерология. 2017. № 2. С. 103-109.
52. Hu J., Liu Z., Wang X. Does TP53 mutation promote ovarian cancer metastasis to omentum by regulating lipid metabolism // Med. Hypotheses. 2013. Vol. 81. P. 515-520.
53. Григорьева И.Н., Ефимова О.В., Тов Н.Л., Суворова Т.С. Значение генетического тестирования при ведении острого и хронического панкреатита различной этиологии // Мед. алфавит. 2016. Т. 3, № 24 (Практическая гастроэнтерология). С. 5-10.
54. Lu S., Ahmed T., Du P., Wang Y. Genomic Variations in Pancreatic Cancer and Potential Opportunities for Development of New Approaches for Diagnosis and Treatment // Int. J. Mol. Sci. 2017. Vol. 18, N 6. Р. 1201.
55. Paschka P., Schlenk R.F., Gaidzik V.I. et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication // J. Clin. Oncol. 2010. Vol. 28, N 22. Р. 3636-3643.
56. Yan H., Parsons D.W., Jin G. et al. IDH1 and IDH2 mutations in gliomas // N. Engl. J. Med. 2009. Vol. 360, N 8. Р. 765-773.
57. Nelson D.L., Cox M.M. Lehninger Principles of biochemistry. Fifth ed. New York: Freeman W.H. and company, 2008. 1158 p. (р. 637).
58. Krantz B. Fatty acid and cholesterol biosynthesis and regulation: University of California, Berkeley MCB 102, Spring 2008, Metabolism Lecture 14 Reading: Ch. 21 of Principles of Biochemistry, «Lipid Biosynthesis.» 452 р.
59. Кольман Я., Рем К.Г. Наглядная биохимия. 4-е
60. изд. М.: БИНОМ. Лаборатория знаний, 2012. 469 с.
61. Liao J., Chung Y.T., Yang A.L. et al. Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice // Mol. Carcinog. 2013. Vol. 52, N 9. Р. 739-750.
62. Miziorko H.M. Enzymes of the mevalonate pathway of isoprenoid biosynthesis // Arch. Biochem. Biophys. 2011. Vol. 505. Р. 131-143.
63. Gao J., Liao J., Yang G.Y. CAAX-box protein, prenylation process and carcinogenesis // Am. J. Transl. Res. 2009. Vol. 1. Р. 312-325.
64. Zhang F.L., Casey P.J. Protein prenylation: molecular mechanisms and functional consequences // Ann. Rev. Biochem. 1996. Vol. 65. Р. 241-269.
65. Wang M., Casey P.J. Protein prenylation: unique fats make their mark on biology // Nat. Rev. Mol. Cell. Biol. 2016. Vol. 17, N 2. Р. 110-122.
66. Winter-Vann A.M., Casey P.J. Post-prenylation-processing enzymes as new targets in oncogenesis // Nat. Rev. Cancer. 2005. Vol. 5, N 5. Р. 405-412.
67. Saxena N., Lahiri S.S., Hambarde S., Tripathi R.P. RAS: target for cancer therapy // Cancer Invest. 2008. Vol. 26, N 9. Р. 948-955.
68. Lowy D.R. Function and regulation of Ras // Ann. Rev. Biochem. 1993. Vol. 62. Р. 851-891.
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Grigorieva I.N., Efimova O.V., Romanova T.I. LIPID METABOLISM DISORDERS In PANCREATIC CANCER. Ateroscleroz. 2017;13(3):43-49. (In Russ.)
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