Oxy hóa axit béo và carnitine palmitoyltransferase I: những mục tiêu điều trị mới nổi trong ung thư

Hanahan D, Weinberg RA . Hallmarks of cancer: the next generation. Cell 2011; 144: 646–674.

Zhao Y, Butler EB, Tan M . Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis 2013; 4: e532.

Bensinger SJ, Christofk HR . New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol 2012; 23: 352–361.

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

Carracedo A, Cantley LC, Pandolfi PP . Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer 2013; 13: 227–232.

Hossain F, Al-Khami AA, Wyczechowska D, Hernandez C, Zheng L, Reiss K et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol Res 2015; 3: 1236–1247.

Ricciardi MR, Mirabilii S, Allegretti M, Licchetta R, Calarco A, Torrisi MR et al. Targeting the leukemia cell metabolism by the CPTIa inhibition: functional pre-clinical effects in leukemias. Blood 2015; 126: 1925–1929.

Yan S, Yang XF, Liu HL, Fu N, Ouyang Y, Qing K . Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol 2015; 21: 3492–3498.

Watkins PA, Maiguel D, Jia Z, Pevsner J . Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J Lipid Res 2007; 48: 2736–2750.

van der Leij FR, Kram AM, Bartelds B, Roelofsen H, Smid GB, Takens J et al. Cytological evidence that the C-terminus of carnitine palmitoyltransferase I is on the cytosolic face of the mitochondrial outer membrane. Biochem J 1999; 341: 777–784.

Rufer AC, Thoma R, Hennig M . Structural insight into function and regulation of carnitine palmitoyltransferase. Cell Mol Life Sci 2009; 66: 2489–2501.

Bonnefont JP, Djouadi F, Prip-Buus C, Gobin S, Munnich A, Bastin J . Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med 2004; 25: 495–520.

Flavin R, Peluso S, Nguyen PL, Loda M . Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol 2010; 6: 551–562.

Schreurs M, Kuipers F, van der Leij FR . Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. Obes Rev 2010; 11: 380–388.

Casals N, Zammit V, Herrero L, Fado R, Rodriguez-Rodriguez R, Serra D . Carnitine palmitoyltransferase 1C: from cognition to cancer. Prog Lipid Res 2015; 61: 134–148.

McGarry JD, Brown NF . The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 1997; 244: 1–14.

Carrasco P, Jacas J, Sahun I, Muley H, Ramirez S, Puisac B et al. Carnitine palmitoyltransferase 1C deficiency causes motor impairment and hypoactivity. Behav Brain Res 2013; 256: 291–297.

Zaugg K, Yao Y, Reilly PT, Kannan K, Kiarash R, Mason J et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev 2011; 25: 1041–1051.

Wolfgang MJ, Lane MD . Control of energy homeostasis: role of enzymes and intermediates of fatty acid metabolism in the central nervous system. Annu Rev Nutr 2006; 26: 23–44.

Sierra AY, Gratacos E, Carrasco P, Clotet J, Urena J, Serra D et al. CPTIc is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. J Biol Chem 2008; 283: 6878–6885.

Wolfgang MJ, Cha SH, Millington DS, Cline G, Shulman GI, Suwa A et al. Brain-specific carnitine palmitoyl-transferase-1c: role in CNS fatty acid metabolism, food intake, and body weight. J Neurochem 2008; 105: 1550–1559.

Casals N, Zammit V, Herrero L, Fado R, Rodriguez-Rodriguez R, Serra D . Carnitine palmitoyltransferase 1C: from cognition to cancer. Prog Lipid Res 2016; 61: 134–148.

Harjes U, Kalucka J, Carmeliet P . Targeting fatty acid metabolism in cancer and endothelial cells. Crit Rev Oncol Hematol 2016; 97: 15–21.

Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY et al. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009; 461: 109–113.

Liu Y . Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis 2006; 9: 230–234.

Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 2012; 22: 547–560.

Monti S, Savage KJ, Kutok JL, Feuerhake F, Kurtin P, Mihm M et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005; 105: 1851–1861.

Pacilli A, Calienni M, Margarucci S, D'Apolito M, Petillo O, Rocchi L et al. Carnitine-acyltransferase system inhibition, cancer cell death, and prevention of myc-induced lymphomagenesis. J Natl Cancer Inst 2013; 105: 489–498.

Cirillo A, Di Salle A, Petillo O, Melone MA, Grimaldi G, Bellotti A et al. High grade glioblastoma is associated with aberrant expression of ZFP57, a protein involved in gene imprinting, and of CPTIA and CPTIC that regulate fatty acid metabolism. Cancer Biol Ther 2014; 15: 735–741.

Pike LS, Smift AL, Croteau NJ, Ferrick DA, Wu M . Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta 2011; 1807: 726–734.

Chiarugi A, Dölle C, Felici R, Ziegler M . The NAD metabolome — a key determinant of cancer cell biology. Nat Rev Cancer 2012; 12: 741–752.

Kawashima I, Mitsumori T, Nozaki Y, Yamamoto T, Shobu-Sueki Y, Nakajima K et al. Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cells. Exp Hematol 2015; 43: 524–533; e521.

Jeon SM, Chandel NS, Hay N . AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 2012; 485: 661–665.

Li J, Zhao S, Zhou X, Zhang T, Zhao L, Miao P et al. Inhibition of lipolysis by mercaptoacetate and etomoxir specifically sensitize drug-resistant lung adenocarcinoma cell to paclitaxel. PLoS One 2013; 8: e74623.

Tung S, Shi Y, Wong K, Zhu F, Gorczynski R, Laister RC et al. PPARalpha and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia. Blood 2013; 122: 969–980.

Kostecka A, Sznarkowska A, Meller K, Acedo P, Shi Y, Mohammad Sakil HA et al. JNK-NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress. Cell Death Dis 2014; 5: e1484.

Bensaad K, Favaro E, Lewis CA, Peck B, Lord S, Collins JM et al. Fatty acid uptake and lipid storage induced by HIF-1alpha contribute to cell growth and survival after hypoxia-reoxygenation. Cell Rep 2014; 9: 349–365.

Huang D, Li T, Li X, Zhang L, Sun L, He X et al. HIF-1-mediated suppression of acyl-CoA dehydrogenases and fatty acid oxidation is critical for cancer progression. Cell Rep 2014; 8: 1930–1942.

Sanchez-Macedo N, Feng J, Faubert B, Chang N, Elia A, Rushing EJ et al. Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ 2013; 20: 659–668.

Vander Heiden MG, Cantley LC, Thompson CB . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 1029–1033.

Zha S, Ferdinandusse S, Hicks JL, Denis S, Dunn TA, Wanders RJ et al. Peroxisomal branched chain fatty acid beta-oxidation pathway is upregulated in prostate cancer. Prostate 2005; 63: 316–323.

Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 2010; 120: 142–156.

Effert PJ, Bares R, Handt S, Wolff JM, Bull U, Jakse G . Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol 1996; 155: 994–998.

Schlaepfer IR, Glode LM, Hitz CA, Pac CT, Boyle KE, Maroni P et al. Inhibition of lipid oxidation increases glucose metabolism and enhances 2-deoxy-2-[(18)F]Fluoro-D-glucose uptake in prostate cancer mouse xenografts. Mol Imaging Biol 2015; 17: 529–538.

Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K . Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res 2013; 52: 585–589.

McGarry JD, Mannaerts GP, Foster DW . A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest 1977; 60: 265–270.

Zadra G, Photopoulos C, Loda M . The fat side of prostate cancer. Biochim Biophys Acta 2013; 1831: 1518–1532.

Abu-Elheiga L, Matzuk MM, Abo-Hashema KA, Wakil SJ . Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 2001; 291: 2613–2616.

Wakil SJ, Abu-Elheiga LA . Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 2009; 50: S138–S143.

Schlaepfer IR, Rider L, Rodrigues LU, Gijon MA, Pac CT, Romero L et al. Lipid catabolism via CPTI as a therapeutic target for prostate cancer. Mol Cancer Ther 2014; 13: 2361–2371.

Tirado-Velez JM, Joumady I, Saez-Benito A, Cozar-Castellano I, Perdomo G . Inhibition of fatty acid metabolism reduces human myeloma cells proliferation. PLoS One 2012; 7: e46484.

Gatza ML, Silva GO, Parker JS, Fan C, Perou CM . An integrated genomics approach identifies drivers of proliferation in luminal-subtype human breast cancer. Nat Genet 2014; 46: 1051–1059.

Linher-Melville K, Zantinge S, Sanli T, Gerstein H, Tsakiridis T, Singh G . Establishing a relationship between prolactin and altered fatty acid beta-oxidation via carnitine palmitoyl transferase 1 in breast cancer cells. BMC Cancer 2011; 11: 56.

Pucci S, Zonetti MJ, Fisco T, Polidoro C, Bocchinfuso G, Palleschi A et al. Carnitine palmitoyl transferase-1A (CPTIA): a new tumor specific target in human breast cancer. Oncotarget 2016; 7: 19982–19996.

Li S, Zhou T, Li C, Dai Z, Che D, Yao Y et al. High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner. PLoS One 2014; 9: e97330.

Roy D, Mondal S, Wang C, He X, Khurana A, Giri S et al. Loss of HSulf-1 promotes altered lipid metabolism in ovarian cancer. Cancer Metab 2014; 2: 13.

Shao H, Mohamed EM, Xu GG, Waters M, Jing K, Ma Y et al. Carnitine palmitoyltransferase 1A functions to repress FoxO transcription factors to allow cell cycle progression in ovarian cancer. Oncotarget 2015; 7: 3832–3846.

Rodriguez-Enriquez S, Hernandez-Esquivel L, Marin-Hernandez A, El Hafidi M, Gallardo-Perez JC, Hernandez-Resendiz I et al. Mitochondrial free fatty acid beta-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int J Biochem Cell Biol 2015; 65: 209–221.

Wakamiya T, Suzuki SO, Hamasaki H, Honda H, Mizoguchi M, Yoshimoto K et al. Elevated expression of fatty acid synthase and nuclear localization of carnitine palmitoyltransferase 1C are common among human gliomas. Neuropathology 2014; 34: 465–474.

de Souza CO, Kurauti MA, de Fatima Silva F, de Morais H, Curi R, Hirabara SM et al. Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats. Cell Physiol Biochem 2015; 36: 1659–1669.

Schlaepfer IR, Nambiar DK, Ramteke A, Kumar R, Dhar D, Agarwal C et al. Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation. Oncotarget 2015; 6: 22836–22856.

Reilly PT, Mak TW . Molecular pathways: tumor cells Co-opt the brain-specific metabolism gene CPTIC to promote survival. Clin Cancer Res 2012; 18: 5850–5855.

Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 2010; 120: 142–156.

Lee EA, Angka L, Rota SG, Hanlon T, Mitchell A, Hurren R et al. Targeting mitochondria with avocatin B induces selective leukemia cell death. Cancer Res 2015; 75: 2478–2488.

Giordano A, Calvani M, Petillo O, Grippo P, Tuccillo F, Melone MA et al. tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1. Cell Death Differ 2005; 12: 603–613.

Paumen MB, Ishida Y, Han H, Muramatsu M, Eguchi Y, Tsujimoto Y et al. Direct interaction of the mitochondrial membrane protein carnitine palmitoyltransferase I with Bcl-2. Biochem Biophys Res Commun 1997; 231: 523–525.

Grosch S, Schiffmann S, Geisslinger G . Chain length-specific properties of ceramides. Prog Lipid Res 2012; 51: 50–62.

Namgaladze D, Lips S, Leiker TJ, Murphy RC, Ekroos K, Ferreiros N et al. Inhibition of macrophage fatty acid β-oxidation exacerbates palmitate-induced inflammatory and endoplasmic reticulum stress responses. Diabetologia 2014; 57: 1067–1077.

Ambros V . microRNAs: tiny regulators with great potential. Cell 2001; 107: 823–826.

O'Driscoll L . The emerging world of microRNAs. Anticancer Res 2006; 26: 4271–4278.

Li XJ, Ren ZJ, Tang JH . MicroRNA-34a: a potential therapeutic target in human cancer. Cell Death Disease 2014; 5: e1327.

Igaz I, Igaz P . Tumor surveillance by circulating microRNAs: a hypothesis. Cell Mol Life Sci 2014; 71: 4081–4087.

Iliopoulos D, Drosatos K, Hiyama Y, Goldberg IJ, Zannis VI . MicroRNA-370 controls the expression of microRNA-122 and CPTIalpha and affects lipid metabolism. J Lipid Res 2010; 51: 1513–1523.

Liu L, Wang YD, Wu J, Cui J, Chen T . Carnitine palmitoyltransferase 1A (CPTIA): a transcriptional target of PAX3-FKHR and mediates PAX3-FKHR-dependent motility in alveolar rhabdomyosarcoma cells. BMC Cancer 2012; 12: 154.

Calhabeu F, Hayashi S, Morgan JE, Relaix F, Zammit PS . Alveolar rhabdomyosarcoma-associated proteins PAX3/FOXO1A and PAX7/FOXO1A suppress the transcriptional activity of MyoD-target genes in muscle stem cells. Oncogene 2013; 32: 651–662.

Jothi M, Nishijo K, Keller C, Mal AK . AKT and PAX3-FKHR cooperation enforces myogenic differentiation blockade in alveolar rhabdomyosarcoma cell. Cell Cycle 2012; 11: 895–908.

Linardic CM . PAX3-FOXO1 fusion gene in rhabdomyosarcoma. Cancer Lett 2008; 270: 10–18.

Kim MS, Lim DY, Kim JE, Chen H, Lubet RA, Dong Z et al. Src is a novel potential off-target of RXR agonists, 9-cis-UAB30 and Targretin, in human breast cancer cells. Mol Carcinog 2014; 54: 1596–1604.

Li J, Chanrion M, Sawey E, Wang T, Chow E, Tward A et al. Reciprocal interaction of Wnt and RXR-alpha pathways in hepatocyte development and hepatocellular carcinoma. PLoS One 2015; 10: e0118480.

Gilardi F, Desvergne B . RXRs: collegial partners. Subcell Biochem 2014; 70: 75–102.

Ishizawa M, Kagechika H, Makishima M . NR4A nuclear receptors mediate carnitine palmitoyltransferase 1A gene expression by the rexinoid HX600. Biochem Biophys Res Commun 2012; 418: 780–785.

Clevenger CV, Furth PA, Hankinson SE, Schuler LA . The role of prolactin in mammary carcinoma. Endocr Rev 2003; 24: 1–27.

Shigemura K, Sung SY, Kubo H, Arnold RS, Fujisawa M, Gotoh A et al. Reactive oxygen species mediate androgen receptor- and serum starvation-elicited downstream signaling of ADAM9 expression in human prostate cancer cells. Prostate 2007; 67: 722–731.

Lin H, Lu JP, Laflamme P, Qiao S, Shayegan B, Bryskin I et al. Inter-related in vitro effects of androgens, fatty acids and oxidative stress in prostate cancer: a mechanistic model supporting prevention strategies. Int J Oncol 2010; 37: 761–766.

Burdelski C, Ruge OM, Melling N, Koop C, Simon R, Steurer S et al. HDAC1 overexpression independently predicts biochemical recurrence and is associated with rapid tumor cell proliferation and genomic instability in prostate cancer. Exp Mol Pathol 2015; 98: 419–426.

Mazzarelli P, Pucci S, Bonanno E, Sesti F, Calvani M, Spagnoli LG . Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation? Cancer Biol Ther 2007; 6: 1606–1613.

Lopaschuk GD, Wall SR, Olley PM, Davies NJ . Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ Res 1988; 63: 1036–1043.

Bristow M . Etomoxir: a new approach to treatment of chronic heart failure. Lancet 2000; 356: 1621–1622.

Ratheiser K, Schneeweiss B, Waldhausl W, Fasching P, Korn A, Nowotny P et al. Inhibition by etomoxir of carnitine palmitoyltransferase I reduces hepatic glucose production and plasma lipids in non-insulin-dependent diabetes mellitus. Metabolism 1991; 40: 1185–1190.

Wolf HP . Possible new therapeutic approach in diabetes mellitus by inhibition of carnitine palmitoyltransferase 1 (CPTI). Horm Metab Res Suppl 1992; 26: 62–67.

Merrill CL, Ni H, Yoon LW, Tirmenstein MA, Narayanan P, Benavides GR et al. Etomoxir-induced oxidative stress in HepG2 cells detected by differential gene expression is confirmed biochemically. Toxicol Sci 2002; 68: 93–101.

Cabrero A, Merlos M, Laguna JC, Carrera MV . Down-regulation of acyl-CoA oxidase gene expression and increased NF-kappaB activity in etomoxir-induced cardiac hypertrophy. J Lipid Res 2003; 44: 388–398.

Ashrafian H, Horowitz JD, Frenneaux MP . Perhexiline. Cardiovasc Drug Rev 2007; 25: 76–97.

Giannessi F, Pessotto P, Tassoni E, Chiodi P, Conti R, De Angelis F et al. Discovery of a long-chain carbamoyl aminocarnitine derivative, a reversible carnitine palmitoyltransferase inhibitor with antiketotic and antidiabetic activity. J Med Chem 2003; 46: 303–309.

Conti R, Mannucci E, Pessotto P, Tassoni E, Carminati P, Giannessi F et al. Selective reversible inhibition of liver carnitine palmitoyl-transferase 1 by teglicar reduces gluconeogenesis and improves glucose homeostasis. Diabetes 2011; 60: 644–651.

Samudio I, Konopleva M . Targeting leukemia's "fatty tooth". Blood 2015; 126: 1874–1875.

Ricciardi MR, Mirabilii S, Allegretti M, Licchetta R, Calarco A, Torrisi MR et al. Targeting the leukemia cell metabolism by the CPTIa inhibition: functional preclinical effects in leukemias. Blood 2015; 126: 1925–1929.

Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 2015; 520: 192–197.

Patella F, Schug ZT, Persi E, Neilson LJ, Erami Z, Avanzato D et al. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol Cell Proteomics 2015; 14: 621–634.