Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Metabolic Remodeling Induced by Adipocytes: A New Achilles' Heel in Invasive Breast Cancer?

Author(s): Camille Attané*, Delphine Milhas, Andrew J. Hoy and Catherine Muller

Volume 27, Issue 24, 2020

Page: [3984 - 4001] Pages: 18

DOI: 10.2174/0929867325666180426165001

Price: $65

Abstract

Metabolic reprogramming represents an important hallmark of cancer cells. Besides de novo fatty acid synthesis, it is now clear that cancer cells can acquire Fatty Acids (FA) from tumor-surrounding adipocytes to increase their invasive capacities. Indeed, adipocytes release FA in response to tumor secreted factors that are transferred to tumor cells to be either stored as triglycerides and other complex lipids or oxidized in mitochondria. Like all cells, FA can be released over time from triglyceride stores through lipolysis and then oxidized in mitochondria in cancer cells. This metabolic interaction results in specific metabolic remodeling in cancer cells, and underpins adipocyte stimulated tumor progression. Lipolysis and fatty acid oxidation therefore represent novel targets of interest in the treatment of cancer. In this review, we summarize the recent advances in our understanding of the metabolic reprogramming induced by adipocytes, with a focus on breast cancer. Then, we recapitulate recent reports studying the effect of lipolysis and fatty acid oxidation inhibitors on tumor cells and discuss the interest to target these metabolic pathways as new therapeutic approaches for cancer.

Keywords: Breast cancer, adipocyte, metabolic remodeling, lipolysis, fatty acid oxidation, obesity, tumor microenvironment.

« Previous Next »
[1]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[2]
DeBerardinis, R.J.; Chandel, N.S. Fundamentals of cancer metabolism. Sci. Adv., 2016, 2(5),e1600200.
[http://dx.doi.org/10.1126/sciadv.1600200] [PMID: 27386546]
[3]
Lehuédé, C.; Dupuy, F.; Rabinovitch, R.; Jones, R.G.; Siegel, P.M. Metabolic plasticity as a determinant of tumor growth and metastasis. Cancer Res., 2016, 76(18), 5201-5208.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0266] [PMID: 27587539]
[4]
Martinez-Outschoorn, U.; Sotgia, F.; Lisanti, M.P. Tumor microenvironment and metabolic synergy in breast cancers: critical importance of mitochondrial fuels and function. Semin. Oncol., 2014, 41(2), 195-216.
[http://dx.doi.org/10.1053/j.seminoncol.2014.03.002] [PMID: 24787293]
[5]
Bojková, B.; Garajová, M.; Kajo, K.; Péc, M.; Kubatka, P.; Kassayová, M.; Kisková, T.; Orendás, P.; Ahlersová, E.; Ahlers, I. Pioglitazone in chemically induced mammary carcinogenesis in rats. Eur. J. Cancer Prev., 2010, 19(5), 379-384.
[http://dx.doi.org/10.1097/CEJ.0b013e32833ca233] [PMID: 20581687]
[6]
Christodoulou, M.I.; Scorilas, A. Metformin and Anticancer therapeutics: hopes for a more enhanced armamentarium against human neoplasias? Curr. Med. Chem., 2017, 24(1), 14-56.
[http://dx.doi.org/10.2174/0929867323666160907161459] [PMID: 27604091]
[7]
Jian-Yu, E.; Graber, J.M.; Lu, S.E.; Lin, Y.; Lu-Yao, G.; Tan, X.L. Effect of metformin and statin use on survival in pancreatic cancer patients: a systematic literature review and meta-analysis. Curr Med Chem, 2018, 25(22), 2595-2607.
[http://dx.doi.org/10.2174/0929867324666170412145232] [PMID: 28403788]
[8]
Tseng, C.H. Rosiglitazone reduces breast cancer risk in Taiwanese female patients with type 2 diabetes mellitus. Oncotarget, 2017, 8(2), 3042-3048.
[http://dx.doi.org/10.18632/oncotarget.13824] [PMID: 27936468]
[9]
Martinez-Outschoorn, U.E.; Peiris-Pagés, M.; Pestell, R.G.; Sotgia, F.; Lisanti, M.P. Cancer metabolism: a therapeutic perspective. Nat. Rev. Clin. Oncol., 2017, 14(1), 11-31.
[http://dx.doi.org/10.1038/nrclinonc.2016.60] [PMID: 27141887]
[10]
Mashima, T.; Seimiya, H.; Tsuruo, T. De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br. J. Cancer, 2009, 100(9), 1369-1372.
[http://dx.doi.org/10.1038/sj.bjc.6605007] [PMID: 19352381]
[11]
Orendáš, P.; Kubatka, P.; Bojková, B.; Kassayová, M.; Kajo, K.; Výbohová, D.; Kružliak, P.; Péč, M.; Adamkov, M.; Kapinová, A.; Adamicová, K.; Sadloňová, V.; Chmelová, M.; Stollárová, N. Melatonin potentiates the anti-tumour effect of pravastatin in rat mammary gland carcinoma model. Int. J. Exp. Pathol., 2014, 95(6), 401-410.
[http://dx.doi.org/10.1111/iep.12094] [PMID: 25270735]
[12]
Clement, E.; Lazar, I.; Muller, C.; Nieto, L. Obesity and melanoma: could fat be fueling malignancy? Pigment Cell Melanoma Res., 2017, 30(3), 294-306.
[http://dx.doi.org/10.1111/pcmr.12584] [PMID: 28222242]
[13]
Laurent, V.; Guérard, A.; Mazerolles, C.; Le Gonidec, S.; Toulet, A.; Nieto, L.; Zaidi, F.; Majed, B.; Garandeau, D.; Socrier, Y.; Golzio, M.; Cadoudal, T.; Chaoui, K.; Dray, C.; Monsarrat, B.; Schiltz, O.; Wang, Y.Y.; Couderc, B.; Valet, P.; Malavaud, B.; Muller, C. Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nat. Commun., 2016, 7, 10230.
[http://dx.doi.org/10.1038/ncomms10230] [PMID: 26756352]
[14]
Wang, Y-Y.; Lehuédé, C.; Laurent, V.; Dirat, B.; Dauvillier, S.; Bochet, L.; Le Gonidec, S.; Escourrou, G.; Valet, P.; Muller, C. Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer. Cancer Lett., 2012, 324(2), 142-151.
[http://dx.doi.org/10.1016/j.canlet.2012.05.019] [PMID: 22643115]
[15]
Andarawewa, K.L.; Motrescu, E.R.; Chenard, M.P.; Gansmuller, A.; Stoll, I.; Tomasetto, C.; Rio, M.C. Stromelysin-3 is a potent negative regulator of adipogenesis participating to cancer cell-adipocyte interaction/crosstalk at the tumor invasive front. Cancer Res., 2005, 65(23), 10862-10871.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1231] [PMID: 16322233]
[16]
Balaban, S.; Shearer, R.F.; Lee, L.S.; van Geldermalsen, M.; Schreuder, M.; Shtein, H.C.; Cairns, R.; Thomas, K.C.; Fazakerley, D.J.; Grewal, T.; Holst, J.; Saunders, D.N.; Hoy, A.J. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab., 2017, 5, 1.
[http://dx.doi.org/10.1186/s40170-016-0163-7] [PMID: 28101337]
[17]
Bochet, L.; Lehuédé, C.; Dauvillier, S.; Wang, Y.Y.; Dirat, B.; Laurent, V.; Dray, C.; Guiet, R.; Maridonneau-Parini, I.; Le Gonidec, S.; Couderc, B.; Escourrou, G.; Valet, P.; Muller, C. Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res., 2013, 73(18), 5657-5668.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0530] [PMID: 23903958]
[18]
Dirat, B.; Bochet, L.; Dabek, M.; Daviaud, D.; Dauvillier, S.; Majed, B.; Wang, Y.Y.; Meulle, A.; Salles, B.; Le Gonidec, S.; Garrido, I.; Escourrou, G.; Valet, P.; Muller, C. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res., 2011, 71(7), 2455-2465.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3323] [PMID: 21459803]
[19]
Nieman, K.M.; Kenny, H.A.; Penicka, C.V.; Ladanyi, A.; Buell-Gutbrod, R.; Zillhardt, M.R.; Romero, I.L.; Carey, M.S.; Mills, G.B.; Hotamisligil, G.S.; Yamada, S.D.; Peter, M.E.; Gwin, K.; Lengyel, E. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med., 2011, 17(11), 1498-1503.
[http://dx.doi.org/10.1038/nm.2492] [PMID: 22037646]
[20]
Wang, Y.Y.; Attané, C.; Milhas, D.; Dirat, B.; Dauvillier, S.; Guerard, A.; Gilhodes, J.; Lazar, I.; Alet, N.; Laurent, V.; Le Gonidec, S.; Biard, D.; Hervé, C.; Bost, F.; Ren, G.S.; Bono, F.; Escourrou, G.; Prentki, M.; Nieto, L.; Valet, P.; Muller, C. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight, 2017, 2(4), e87489.
[http://dx.doi.org/10.1172/jci.insight.87489] [PMID: 28239646]
[21]
D’Esposito, V.; Passaretti, F.; Hammarstedt, A.; Liguoro, D.; Terracciano, D.; Molea, G.; Canta, L.; Miele, C.; Smith, U.; Beguinot, F.; Formisano, P. Adipocyte-released insulinlike growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro. Diabetologia, 2012, 55(10), 2811-2822.
[http://dx.doi.org/10.1007/s00125-012-2629-7] [PMID: 22798065]
[22]
Lapeire, L.; Hendrix, A.; Lambein, K.; Van Bockstal, M.; Braems, G.; Van Den Broecke, R.; Limame, R.; Mestdagh, P.; Vandesompele, J.; Vanhove, C.; Maynard, D.; Lehuédé, C.; Muller, C.; Valet, P.; Gespach, C.P.; Bracke, M.; Cocquyt, V.; Denys, H.; De Wever, O. Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling. Cancer Res., 2014, 74(23), 6806-6819.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0160] [PMID: 25252914]
[23]
Wang, C.; Gao, C.; Meng, K.; Qiao, H.; Wang, Y. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2. PLoS One, 2015, 10(3), e0119348.
[http://dx.doi.org/10.1371/journal.pone.0119348] [PMID: 25747684]
[24]
Rowan, B.G.; Gimble, J.M.; Sheng, M.; Anbalagan, M.; Jones, R.K.; Frazier, T.P.; Asher, M.; Lacayo, E.A.; Friedlander, P.L.; Kutner, R.; Chiu, E.S. Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS One, 2014, 9(2),e89595.
[http://dx.doi.org/10.1371/journal.pone.0089595] [PMID: 24586900]
[25]
Park, J.; Euhus, D.M.; Scherer, P.E. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr. Rev., 2011, 32(4), 550-570.
[http://dx.doi.org/10.1210/er.2010-0030] [PMID: 21642230]
[26]
Calle, E.E.; Kaaks, R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer, 2004, 4(8), 579-591.
[http://dx.doi.org/10.1038/nrc1408] [PMID: 15286738]
[27]
Calle, E.E.; Rodriguez, C.; Walker-Thurmond, K.; Thun, M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med., 2003, 348(17), 1625-1638.
[http://dx.doi.org/10.1056/NEJMoa021423] [PMID: 12711737]
[28]
Feola, A.; Ricci, S.; Kouidhi, S.; Rizzo, A.; Penon, A.; Formisano, P.; Giordano, A.; Di Carlo, A.; Di Domenico, M. Multifaceted breast cancer: the molecular connection with obesity. J. Cell. Physiol., 2017, 232(1), 69-77.
[http://dx.doi.org/10.1002/jcp.25475] [PMID: 27363538]
[29]
Park, J.; Morley, T.S.; Kim, M.; Clegg, D.J.; Scherer, P.E. Obesity and cancer--mechanisms underlying tumour progression and recurrence. Nat. Rev. Endocrinol., 2014, 10(8), 455-465.
[http://dx.doi.org/10.1038/nrendo.2014.94] [PMID: 24935119]
[30]
Ouchi, N.; Parker, J.L.; Lugus, J.J.; Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol., 2011, 11(2), 85-97.
[http://dx.doi.org/10.1038/nri2921] [PMID: 21252989]
[31]
Lazar, I.; Clement, E.; Dauvillier, S.; Milhas, D.; DucouxPetit, M.; LeGonidec, S.; Moro, C.; Soldan, V.; Dalle, S.; Balor, S.; Golzio, M.; Burlet-Schiltz, O.; Valet, P.; Muller, C.; Nieto, L. Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer. Cancer Res., 2016, 76(14), 4051-4057.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0651] [PMID: 27216185]
[32]
Krawczyk, S.A.; Haller, J.F.; Ferrante, T.; Zoeller, R.A.; Corkey, B.E. Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes. PLoS One, 2012, 7(4), e34904.
[http://dx.doi.org/10.1371/journal.pone.0034904] [PMID: 22493722]
[33]
Policastro, L.L.; Ibañez, I.L.; Notcovich, C.; Duran, H.A.; Podhajcer, O.L. The tumor microenvironment: characterization, redox considerations, and novel approaches for reactive oxygen species-targeted gene therapy. Antioxid. Redox Signal., 2013, 19(8), 854-895.
[http://dx.doi.org/10.1089/ars.2011.4367] [PMID: 22794113]
[34]
Bensaad, K.; Favaro, E.; Lewis, C.A.; Peck, B.; Lord, S.; Collins, J.M.; Pinnick, K.E.; Wigfield, S.; Buffa, F.M.; Li, J.L.; Zhang, Q.; Wakelam, M.J.O.; Karpe, F.; Schulze, A.; Harris, A.L. Fatty acid uptake and lipid storage induced by HIF-1 contribute to cell growth and survival after hypoxiareoxygenation. Cell Rep., 2014, 9(1), 349-365.
[http://dx.doi.org/10.1016/j.celrep.2014.08.056] [PMID: 25263561]
[35]
Guaita-Esteruelas, S.; Guma, J.; Masana, L.; Borras, J. The peritumoural adipose tissue microenvironment and cancer.The roles of fatty acid binding protein 4 and fatty acid binding protein 5. Mol. Cell. Endocrinol., 2018, 462( Pt B), 107-118.
[http://dx.doi.org/10.1016/j.mce.2017.02.002] [PMID: 28163102]
[36]
Kuemmerle, N.B.; Rysman, E.; Lombardo, P.S.; Flanagan, A.J.; Lipe, B.C.; Wells, W.A.; Pettus, J.R.; Froehlich, H.M.; Memoli, V.A.; Morganelli, P.M.; Swinnen, J.V.; Timmerman, L.A.; Chaychi, L.; Fricano, C.J.; Eisenberg, B.L.; Coleman, W.B.; Kinlaw, W.B. Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol. Cancer Ther., 2011, 10(3), 427-436.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0802] [PMID: 21282354]
[37]
Pascual, G.; Avgustinova, A.; Mejetta, S.; Martín, M.; Castellanos, A.; Attolini, C.S.; Berenguer, A.; Prats, N.; Toll, A.; Hueto, J.A.; Bescós, C.; Di Croce, L.; Benitah, S.A. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature, 2017, 541(7635), 41-45.
[http://dx.doi.org/10.1038/nature20791] [PMID: 27974793]
[38]
Beloribi-Djefaflia, S.; Vasseur, S.; Guillaumond, F. Lipid metabolic reprogramming in cancer cells. Oncogenesis, 2016, 5, e189.
[http://dx.doi.org/10.1038/oncsis.2015.49] [PMID: 26807644]
[39]
Koizume, S.; Miyagi, Y. Lipid droplets: a key cellular organelle associated with cancer cell survival under normoxia and hypoxia. Int. J. Mol. Sci., 2016, 17(9), pii: E1430.
[http://dx.doi.org/10.3390/ijms17091430] [PMID: 27589734]
[40]
Zhao, S.; Mugabo, Y.; Iglesias, J.; Xie, L.; Delghingaro-Augusto, V.; Lussier, R.; Peyot, M.L.; Joly, E.; Taïb, B.; Davis, M.A.; Brown, J.M.; Abousalham, A.; Gaisano, H.; Madiraju, S.R.; Prentki, M. α/β-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion. Cell Metab., 2014, 19(6), 993-1007.
[http://dx.doi.org/10.1016/j.cmet.2014.04.003] [PMID: 24814481]
[41]
Zechner, R. FAT FLUX: enzymes, regulators, and pathophysiology of intracellular lipolysis. EMBO Mol. Med., 2015, 7(4), 359-362.
[http://dx.doi.org/10.15252/emmm.201404846] [PMID: 25604059]
[42]
Nomura, D.K.; Long, J.Z.; Niessen, S.; Hoover, H.S.; Ng, S.W.; Cravatt, B.F. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell, 2010, 140(1), 49-61.
[http://dx.doi.org/10.1016/j.cell.2009.11.027] [PMID: 20079333]
[43]
Yim, C.Y.; Sekula, D.J.; Hever-Jardine, M.P.; Liu, X.; Warzecha, J.M.; Tam, J.; Freemantle, S.J.; Dmitrovsky, E.; Spinella, M.J. G0S2 suppresses oncogenic transformation by repressing a MYC-regulated transcriptional program. Cancer Res., 2016, 76(5), 1204-1213.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2265] [PMID: 26837760]
[44]
Zagani, R.; El-Assaad, W.; Gamache, I.; Teodoro, J.G. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells. Oncotarget, 2015, 6(29), 28282-28295.
[http://dx.doi.org/10.18632/oncotarget.5061] [PMID: 26318046]
[45]
Carracedo, A.; Cantley, L.C.; Pandolfi, P.P. Cancer metabolism: fatty acid oxidation in the limelight. Nat. Rev. Cancer, 2013, 13(4), 227-232.
[http://dx.doi.org/10.1038/nrc3483] [PMID: 23446547]
[46]
Wen, Y.A.; Xing, X.; Harris, J.W.; Zaytseva, Y.Y.; Mitov, M.I.; Napier, D.L.; Weiss, H.L.; Mark Evers, B.; Gao, T. Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer. Cell Death Dis., 2017, 8(2),e2593.
[http://dx.doi.org/10.1038/cddis.2017.21] [PMID: 28151470]
[47]
Samudio, I.; Harmancey, R.; Fiegl, M.; Kantarjian, H.; Konopleva, M.; Korchin, B.; Kaluarachchi, K.; Bornmann, W.; Duvvuri, S.; Taegtmeyer, H.; Andreeff, M. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J. Clin. Invest., 2010, 120(1), 142-156.
[http://dx.doi.org/10.1172/JCI38942] [PMID: 20038799]
[48]
LeBleu, V.S.; O’Connell, J.T.; Gonzalez Herrera, K.N.; Wikman, H.; Pantel, K.; Haigis, M.C.; de Carvalho, F.M.; Damascena, A.; Domingos Chinen, L.T.; Rocha, R.M.; Asara, J.M.; Kalluri, R. PGC-1 mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat. Cell Biol., 2014, 16( 10), 992-1003,1-15.
[http://dx.doi.org/10.1038/ncb3039] [PMID: 25241037]
[49]
Ayyasamy, V.; Owens, K.M.; Desouki, M.M.; Liang, P.; Bakin, A.; Thangaraj, K.; Buchsbaum, D.J.; LoBuglio, A.F.; Singh, K.K. Cellular model of Warburg effect identifies tumor promoting function of UCP2 in breast cancer and its suppression by genipin. PLoS One, 2011, 6(9), 24792.
[http://dx.doi.org/10.1371/journal.pone.0024792] [PMID: 21935467]
[50]
Sánchez-Aragó, M.; Formentini, L.; Martínez-Reyes, I.; García-Bermudez, J.; Santacatterina, F.; Sánchez-Cenizo, L.; Willers, I.M.; Aldea, M.; Nájera, L.; Juarránz, A.; López, E.C.; Clofent, J.; Navarro, C.; Espinosa, E.; Cuezva, J.M. Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers. Oncogenesis, 2013, 2,e46.
[http://dx.doi.org/10.1038/oncsis.2013.9] [PMID: 23608753]
[51]
Samudio, I.; Fiegl, M.; McQueen, T.; Clise-Dwyer, K.; Andreeff, M. The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res., 2008, 68(13), 5198-5205.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0555] [PMID: 18593920]
[52]
Jiang, L.; Qiu, W.; Zhou, Y.; Wen, P.; Fang, L.; Cao, H.; Zen, K.; He, W.; Zhang, C.; Dai, C.; Yang, J. A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-β1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis. Kidney Int., 2013, 84(2), 285-296.
[http://dx.doi.org/10.1038/ki.2013.80] [PMID: 23515048]
[53]
McDonnell, E.; Crown, S.B.; Fox, D.B.; Kitir, B.; Ilkayeva, O.R.; Olsen, C.A.; Grimsrud, P.A.; Hirschey, M.D. Lipids reprogram metabolism to become a major carbon source for histone acetylation. Cell Rep., 2016, 17(6), 1463-1472.
[http://dx.doi.org/10.1016/j.celrep.2016.10.012] [PMID: 27806287]
[54]
Pietrocola, F.; Galluzzi, L.; Bravo-San Pedro, J.M.; Madeo, F.; Kroemer, G.; Acetyl Coenzyme, A. Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab., 2015, 21(6), 805-821.
[http://dx.doi.org/10.1016/j.cmet.2015.05.014] [PMID: 26039447]
[55]
Viale, A.; Pettazzoni, P.; Lyssiotis, C.A.; Ying, H.; Sánchez, N.; Marchesini, M.; Carugo, A.; Green, T.; Seth, S.; Giuliani, V.; Kost-Alimova, M.; Muller, F.; Colla, S.; Nezi, L.; Genovese, G.; Deem, A.K.; Kapoor, A.; Yao, W.; Brunetto, E.; Kang, Y.; Yuan, M.; Asara, J.M.; Wang, Y.A.; Heffernan, T.P.; Kimmelman, A.C.; Wang, H.; Fleming, J.B.; Cantley, L.C.; DePinho, R.A.; Draetta, G.F. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature, 2014, 514(7524), 628-632.
[http://dx.doi.org/10.1038/nature13611] [PMID: 25119024]
[56]
Havas, K.M.; Milchevskaya, V.; Radic, K.; Alladin, A.; Kafkia, E.; Garcia, M.; Stolte, J.; Klaus, B.; Rotmensz, N.; Gibson, T.J.; Burwinkel, B.; Schneeweiss, A.; Pruneri, G.; Patil, K.R.; Sotillo, R.; Jechlinger, M. Metabolic shifts in residual breast cancer drive tumor recurrence. J. Clin. Invest., 2017, 127(6), 2091-2105.
[http://dx.doi.org/10.1172/JCI89914] [PMID: 28504653]
[57]
Farge, T.; Saland, E.; de Toni, F.; Aroua, N.; Hosseini, M.; Perry, R.; Bosc, C.; Sugita, M.; Stuani, L.; Fraisse, M.; Scotland, S.; Larrue, C.; Boutzen, H.; Féliu, V.; Nicolau-Travers, M.L.; Cassant-Sourdy, S.; Broin, N.; David, M.; Serhan, N.; Sarry, A.; Tavitian, S.; Kaoma, T.; Vallar, L.; Iacovoni, J.; Linares, L.K.; Montersino, C.; Castellano, R.; Griessinger, E.; Collette, Y.; Duchamp, O.; Barreira, Y.; Hirsch, P.; Palama, T.; Gales, L.; Delhommeau, F.; Garmy-Susini, B.H.; Portais, J.C.; Vergez, F.; Selak, M.; Danet-Desnoyers, G.; Carroll, M.; Récher, C.; Sarry, J.E. Chemotherapy resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov., 2017, 7(7), 716-735.
[http://dx.doi.org/10.1158/2159-8290.CD-16-0441] [PMID: 28416471]
[58]
Harper, M.E.; Antoniou, A.; Villalobos-Menuey, E.; Russo, A.; Trauger, R.; Vendemelio, M.; George, A.; Bartholomew, R.; Carlo, D.; Shaikh, A.; Kupperman, J.; Newell, E.W.; Bespalov, I.A.; Wallace, S.S.; Liu, Y.; Rogers, J.R.; Gibbs, G.L.; Leahy, J.L.; Camley, R.E.; Melamede, R.; Newell, M.K. Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J., 2002, 16(12), 1550-1557.
[http://dx.doi.org/10.1096/fj.02-0541com] [PMID: 12374777]
[59]
Bochet, L.; Meulle, A.; Imbert, S.; Salles, B.; Valet, P.; Muller, C. Cancer-associated adipocytes promotes breast tumor radioresistance. Biochem. Biophys. Res. Commun., 2011, 411(1), 102-106.
[http://dx.doi.org/10.1016/j.bbrc.2011.06.101] [PMID: 21712027]
[60]
Duong, M.N.; Cleret, A.; Matera, E.L.; Chettab, K.; Mathé, D.; Valsesia-Wittmann, S.; Clémenceau, B.; Dumontet, C. Adipose cells promote resistance of breast cancer cells to trastuzumab-mediated antibody-dependent cellular cytotoxicity. Breast Cancer Res., 2015, 17, 57.
[http://dx.doi.org/10.1186/s13058-015-0569-0] [PMID: 25908175]
[61]
El Bouhtoury, F.; Keller, J.M.; Colin, S.; Parache, R.M.; Dauça, M. Peroxisomal enzymes in normal and tumoral human breast. J. Pathol., 1992, 166(1), 27-35.
[http://dx.doi.org/10.1002/path.1711660106] [PMID: 1538272]
[62]
Camarda, R.; Zhou, A.Y.; Kohnz, R.A.; Balakrishnan, S.; Mahieu, C.; Anderton, B.; Eyob, H.; Kajimura, S.; Tward, A.; Krings, G.; Nomura, D.K.; Goga, A. Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat. Med., 2016, 22(4), 427-432.
[http://dx.doi.org/10.1038/nm.4055] [PMID: 26950360]
[63]
Pucci, S.; Zonetti, M.J.; Fisco, T.; Polidoro, C.; Bocchinfuso, G.; Palleschi, A.; Novelli, G.; Spagnoli, L.G.; Mazzarelli, P. Carnitine palmitoyl transferase-1A (CPT1A): a new tumor specific target in human breast cancer. Oncotarget, 2016, 7(15), 19982-19996.
[http://dx.doi.org/10.18632/oncotarget.6964] [PMID: 26799588]
[64]
Zaugg, K.; Yao, Y.; Reilly, P.T.; Kannan, K.; Kiarash, R.; Mason, J.; Huang, P.; Sawyer, S.K.; Fuerth, B.; Faubert, B.; Kalliomäki, T.; Elia, A.; Luo, X.; Nadeem, V.; Bungard, D.; Yalavarthi, S.; Growney, J.D.; Wakeham, A.; Moolani, Y.; Silvester, J.; Ten, A.Y.; Bakker, W.; Tsuchihara, K.; Berger, S.L.; Hill, R.P.; Jones, R.G.; Tsao, M.; Robinson, M.O.; Thompson, C.B.; Pan, G.; Mak, T.W. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev., 2011, 25(10), 1041-1051.
[http://dx.doi.org/10.1101/gad.1987211] [PMID: 21576264]
[65]
Holliday, D.L.; Speirs, V. Choosing the right cell line for breast cancer research. Breast Cancer Res., 2011, 13(4), 215.
[http://dx.doi.org/10.1186/bcr2889] [PMID: 21884641]
[66]
Rhodes, D.R.; Yu, J.; Shanker, K.; Deshpande, N.; Varambally, R.; Ghosh, D.; Barrette, T.; Pandey, A.; Chinnaiyan, A.M. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia, 2004, 6(1), 1-6.
[http://dx.doi.org/10.1016/S1476-5586(04)80047-2] [PMID: 15068665]
[67]
Monaco, M.E. Fatty acid metabolism in breast cancer subtypes. Oncotarget, 2017, 8(17), 29487-29500.
[http://dx.doi.org/10.18632/oncotarget.15494] [PMID: 28412757]
[68]
Santander, A.M.; Lopez-Ocejo, O.; Casas, O.; Agostini, T.; Sanchez, L.; Lamas-Basulto, E.; Carrio, R.; Cleary, M.P.; Gonzalez-Perez, R.R.; Torroella-Kouri, M. Paracrine interactions between adipocytes and tumor cells recruit and modify macrophages to the mammary tumor microenvironment: the role of obesity and inflammation in breast adipose tissue. Cancers (Basel), 2015, 7(1), 143-178.
[http://dx.doi.org/10.3390/cancers7010143] [PMID: 25599228]
[69]
Das, S.K.; Eder, S.; Schauer, S.; Diwoky, C.; Temmel, H.; Guertl, B.; Gorkiewicz, G.; Tamilarasan, K.P.; Kumari, P.; Trauner, M.; Zimmermann, R.; Vesely, P.; Haemmerle, G.; Zechner, R.; Hoefler, G. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science, 2011, 333(6039), 233-238.
[http://dx.doi.org/10.1126/science.1198973] [PMID: 21680814]
[70]
Schweiger, M.; Romauch, M.; Schreiber, R.; Grabner, G.F.; Hütter, S.; Kotzbeck, P.; Benedikt, P.; Eichmann, T.O.; Yamada, S.; Knittelfelder, O.; Diwoky, C.; Doler, C.; Mayer, N.; De Cecco, W.; Breinbauer, R.; Zimmermann, R.; Zechner, R. Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nat. Commun., 2017, 8, 14859.
[http://dx.doi.org/10.1038/ncomms14859] [PMID: 28327588]
[71]
Mayer, N.; Schweiger, M.; Romauch, M.; Grabner, G.F.; Eichmann, T.O.; Fuchs, E.; Ivkovic, J.; Heier, C.; Mrak, I.; Lass, A.; Höfler, G.; Fledelius, C.; Zechner, R.; Zimmermann, R.; Breinbauer, R. Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat. Chem. Biol., 2013, 9(12), 785-787.
[http://dx.doi.org/10.1038/nchembio.1359] [PMID: 24096302]
[72]
Ye, L.; Zhang, B.; Seviour, E.G.; Tao, K.X.; Liu, X.H.; Ling, Y.; Chen, J.Y.; Wang, G.B. Monoacylglycerol lipase (MAGL) knockdown inhibits tumor cells growth in colorectal cancer. Cancer Lett., 2011, 307(1), 6-17.
[http://dx.doi.org/10.1016/j.canlet.2011.03.007] [PMID: 21543155]
[73]
Nomura, D.K.; Lombardi, D.P.; Chang, J.W.; Niessen, S.; Ward, A.M.; Long, J.Z.; Hoover, H.H.; Cravatt, B.F. Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem. Biol., 2011, 18(7), 846-856.
[http://dx.doi.org/10.1016/j.chembiol.2011.05.009] [PMID: 21802006]
[74]
Zhang, J.; Liu, Z.; Lian, Z.; Liao, R.; Chen, Y.; Qin, Y.; Wang, J.; Jiang, Q.; Wang, X.; Gong, J. Monoacylglycerol lipase: a novel potential therapeutic target and prognostic indicator for hepatocellular carcinoma. Sci. Rep., 2016, 6, 35784.
[http://dx.doi.org/10.1038/srep35784] [PMID: 27767105]
[75]
Pagano, E.; Borrelli, F.; Orlando, P.; Romano, B.; Monti, M.; Morbidelli, L.; Aviello, G.; Imperatore, R.; Capasso, R.; Piscitelli, F.; Buono, L.; Di Marzo, V.; Izzo, A.A. Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis. Pharmacol. Res., 2017, 119, 227-236.
[http://dx.doi.org/10.1016/j.phrs.2017.02.002] [PMID: 28193521]
[76]
Liu, Q.; Luo, Q.; Halim, A.; Song, G. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer. Cancer Lett., 2017, 401, 39-45.
[http://dx.doi.org/10.1016/j.canlet.2017.05.002] [PMID: 28527945]
[77]
Kobayashi, H.; Nishimura, H.; Matsumoto, K.; Yoshida, M. Identification of the determinants of 2-deoxyglucose sensitivity in cancer cells by shRNA library screening. Biochem. Biophys. Res. Commun., 2015, 467(1), 121-127.
[http://dx.doi.org/10.1016/j.bbrc.2015.09.106] [PMID: 26403972]
[78]
Tisdale, M.J. Cachexia in cancer patients. Nat. Rev. Cancer, 2002, 2(11), 862-871.
[http://dx.doi.org/10.1038/nrc927] [PMID: 12415256]
[79]
Ma, M.; Bai, J.; Ling, Y.; Chang, W.; Xie, G.; Li, R.; Wang, G.; Tao, K. Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells. Mol. Med. Rep., 2016, 13(3), 2850-2856.
[http://dx.doi.org/10.3892/mmr.2016.4829] [PMID: 26847687]
[80]
Jin, J.; Huang, S.; Wang, L.; Leng, Y.; Lu, W. Design and synthesis of Atglistatin derivatives as adipose triglyceride lipase inhibitors. Chem. Biol. Drug Des., 2017, 90(6), 1122-1133.
[http://dx.doi.org/10.1111/cbdd.13029] [PMID: 28548386]
[81]
Inglis, S.; Stewart, S. Metabolic therapeutics in angina pectoris: history revisited with perhexiline. Eur. J. Cardiovasc. Nurs., 2006, 5(2), 175-84.
[http://dx.doi.org/10.1016/j.ejcnurse.2006.01.001] [PMID: 16469541]
[82]
Samudio, I.; Konopleva, M. Targeting leukemia’s “fatty tooth”. Blood, 2015, 126(16), 1874-1875.
[http://dx.doi.org/10.1182/blood-2015-08-665125] [PMID: 26472736]
[83]
Rodríguez-Enríquez, S.; Hernández-Esquivel, L.; Marín-Hernández, A.; El Hafidi, M.; Gallardo-Pérez, J.C.; Hernández-Reséndiz, I.; Rodríguez-Zavala, J.S.; Pacheco-Velázquez, S.C.; Moreno-Sánchez, R. Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int. J. Biochem. Cell Biol., 2015, 65, 209-221.
[http://dx.doi.org/10.1016/j.biocel.2015.06.010] [PMID: 26073129]
[84]
Pucer, A.; Brglez, V.; Payré, C.; Pungerčar, J.; Lambeau, G.; Petan, T. Group X secreted phospholipase A(2) induces lipid droplet formation and prolongs breast cancer cell survival. Mol. Cancer, 2013, 12(1), 111.
[http://dx.doi.org/10.1186/1476-4598-12-111] [PMID: 24070020]
[85]
Ren, X-R.; Wang, J.; Osada, T.; Mook, R.A., Jr; Morse, M.A.; Barak, L.S.; Lyerly, H.K.; Chen, W. Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth. Breast Cancer Res., 2015, 17, 20.
[http://dx.doi.org/10.1186/s13058-015-0528-9] [PMID: 25849870]
[86]
Foster, B.J.; Grotzinger, K.R.; McKoy, W.M.; Rubinstein, L.V.; Hamilton, T.C. Modulation of induced resistance to adriamycin in two human breast cancer cell lines with tamoxifen or perhexiline maleate. Cancer Chemother. Pharmacol., 1988, 22(2), 147-152.
[http://dx.doi.org/10.1007/BF00257313] [PMID: 3409446]
[87]
Qian, J.; Chen, Y.; Meng, T.; Ma, L.; Meng, L.; Wang, X.; Yu, T.; Zask, A.; Shen, J.; Yu, K. Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget, 2016, 7(41), 67071-67086.
[http://dx.doi.org/10.18632/oncotarget.11490] [PMID: 27563814]
[88]
Thupari, J.N.; Pinn, M.L.; Kuhajda, F.P. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA induced inhibition of fatty acid oxidation and cytotoxicity. Biochem. Biophys. Res. Commun., 2001, 285(2), 217-223.
[http://dx.doi.org/10.1006/bbrc.2001.5146] [PMID: 11444828]
[89]
Driffort, V.; Gillet, L.; Bon, E.; Marionneau-Lambot, S.; Oullier, T.; Joulin, V.; Collin, C.; Pagès, J.C.; Jourdan, M.L.; Chevalier, S.; Bougnoux, P.; Le Guennec, J.Y.; Besson, P.; Roger, S. Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization. Mol. Cancer, 2014, 13, 264.
[http://dx.doi.org/10.1186/1476-4598-13-264] [PMID: 25496128]
[90]
Park, J.H.; Vithayathil, S.; Kumar, S.; Sung, P.L.; Dobrolecki, L.E.; Putluri, V.; Bhat, V.B.; Bhowmik, S.K.; Gupta, V.; Arora, K.; Wu, D.; Tsouko, E.; Zhang, Y.; Maity, S.; Donti, T.R.; Graham, B.H.; Frigo, D.E.; Coarfa, C.; Yotnda, P.; Putluri, N.; Sreekumar, A.; Lewis, M.T.; Creighton, C.J.; Wong, L.C.; Kaipparettu, B.A. Fatty acid oxidation-driven src links mitochondrial energy reprogramming and oncogenic properties in triple negative breast cancer. Cell Rep., 2016, 14(9), 2154-2165.
[http://dx.doi.org/10.1016/j.celrep.2016.02.004] [PMID: 26923594]
[91]
Flaig, T.W.; Salzmann-Sullivan, M.; Su, L.J.; Zhang, Z.; Joshi, M.; Gijón, M.A.; Kim, J.; Arcaroli, J.J.; Van Bokhoven, A.; Lucia, M.S.; La Rosa, F.G.; Schlaepfer, I.R. Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade. Oncotarget, 2017, 8(34), 56051-56065.
[http://dx.doi.org/10.18632/oncotarget.17359] [PMID: 28915573]
[92]
Schlaepfer, I.R.; Rider, L.; Rodrigues, L.U.; Gijón, M.A.; Pac, C.T.; Romero, L.; Cimic, A.; Sirintrapun, S.J.; Glodé, L.M.; Eckel, R.H.; Cramer, S.D. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. Mol. Cancer Ther., 2014, 13(10), 2361-2371.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0183] [PMID: 25122071]
[93]
Liu, P.P.; Liu, J.; Jiang, W.Q.; Carew, J.S.; Ogasawara, M.A.; Pelicano, H.; Croce, C.M.; Estrov, Z.; Xu, R.H.; Keating, M.J.; Huang, P. Elimination of chronic lymphocytic leukemia cells in stromal microenvironment by targeting CPT with an antiangina drug perhexiline. Oncogene, 2016, 35(43), 5663-5673.
[http://dx.doi.org/10.1038/onc.2016.103] [PMID: 27065330]
[94]
Pike, L.S.; Smift, A.L.; Croteau, N.J.; Ferrick, D.A.; 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(6), 726-734.
[http://dx.doi.org/10.1016/j.bbabio.2010.10.022] [PMID: 21692241]
[95]
Galluzzi, L.; Kepp, O.; Vander Heiden, M.G.; Kroemer, G. Metabolic targets for cancer therapy. Nat. Rev. Drug Discov., 2013, 12(11), 829-846.
[http://dx.doi.org/10.1038/nrd4145] [PMID: 24113830]
[96]
Tallarico, D.; Rizzo, V.; Di Maio, F.; Petretto, F.; Bianco, G.; Placanica, G.; Marziali, M.; Paravati, V.; Gueli, N.; Meloni, F.; Campbell, S.V. Myocardial cytoprotection by trimetazidine against anthracycline-induced cardiotoxicity in anticancer chemotherapy. Angiology, 2003, 54(2), 219-227.
[http://dx.doi.org/10.1177/000331970305400212] [PMID: 12678198]
[97]
Lestuzzi, C.; Crivellari, D.; Rigo, F.; Viel, E.; Meneguzzo, N. Capecitabine cardiac toxicity presenting as effort angina: a case report. J. Cardiovasc. Med. (Hagerstown), 2010, 11(9), 700-703.
[http://dx.doi.org/10.2459/JCM.0b013e328332e873] [PMID: 20093950]
[98]
Schlaepfer, I.R.; Glodé, L.M.; Hitz, C.A.; Pac, C.T.; Boyle, K.E.; Maroni, P.; Deep, G.; Agarwal, R.; Lucia, S.M.; Cramer, S.D.; Serkova, N.J.; Eckel, R.H. 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(4), 529-538.
[http://dx.doi.org/10.1007/s11307-014-0814-4] [PMID: 25561013]
[99]
Holubarsch, C.J.; Rohrbach, M.; Karrasch, M.; Boehm, E.; Polonski, L.; Ponikowski, P.; Rhein, S. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. Clin. Sci. (Lond.), 2007, 113(4), 205-212.
[http://dx.doi.org/10.1042/CS20060307] [PMID: 17319797]
[100]
Ashrafian, H.; Horowitz, J.D.; Frenneaux, M.P. Perhexiline. Cardiovasc. Drug Rev., 2007, 25(1), 76-97.
[http://dx.doi.org/10.1111/j.1527-3466.2007.00006.x] [PMID: 17445089]
[101]
Suckow, M.A.; Gutierrez, L.S.; Risatti, C.A.; Wolter, W.R.; Taylor, R.E.; Pollard, M.; Navari, R.M.; Castellino, F.J.; Paoni, N.F. The anti-ischemia agent ranolazine promotes the development of intestinal tumors in APC(Min/+) mice. Cancer Lett., 2004, 209(2), 165-169.
[http://dx.doi.org/10.1016/j.canlet.2004.01.007] [PMID: 15159018]
[102]
Zaidi, N.; Lupien, L.; Kuemmerle, N.B.; Kinlaw, W.B.; Swinnen, J.V.; Smans, K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog. Lipid Res., 2013, 52(4), 585-589.
[http://dx.doi.org/10.1016/j.plipres.2013.08.005] [PMID: 24001676]

Rights & Permissions Print Cite
Article Metrics
64
10
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy