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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Review Article

癌症干细胞异常脂质代谢在癌症进展中的作用

卷 21, 期 8, 2021

发表于: 16 March, 2021

页: [631 - 639] 页: 9

弟呕挨: 10.2174/1568009619666210316112333

价格: $65

Open Access Journals Promotions 2
摘要

癌症干细胞 (CSC) 代表一小群能够自我更新和引发肿瘤的癌细胞，它们经历表观遗传、上皮间充质、免疫和代谢重编程以适应肿瘤微环境并在宿主防御或 治疗性侮辱。 众所周知，伴随癌症发作的代谢重编程对于疾病的发病机制至关重要。 在几乎所有癌症类型中都观察到脂质代谢的协调失调。 除了满足膜合成结构脂质的基本要求外，脂质还起着重要的信号分子的作用，并有助于能量稳态。 在这篇综述中，我们总结了癌症进展中 CSC 异常脂质代谢这一有吸引力的研究领域的当前进展，这为基于 CSC 调节脂质代谢的治疗药物提供了见解。

关键词: 癌症干细胞 (CSC)、脂质代谢、癌症进展、肿瘤微环境、脂质代谢失调、能量稳态。

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[1]
Batlle, E.; Clevers, H. Cancer stem cells revisited. Nat. Med., 2017, 23(10), 1124-1134.
[http://dx.doi.org/10.1038/nm.4409] [PMID: 28985214]
[2]
Prieto-Vila, M.; Takahashi, R.U.; Usuba, W.; Kohama, I.; Ochiya, T. Drug resistance driven by cancer stem cells and their niche. Int. J. Mol. Sci., 2017, 18(12), 2574.
[http://dx.doi.org/10.3390/ijms18122574] [PMID: 29194401]
[3]
Lytle, N.K.; Barber, A.G.; Reya, T. Stem cell fate in cancer growth, progression and therapy resistance. Nat. Rev. Cancer, 2018, 18(11), 669-680.
[http://dx.doi.org/10.1038/s41568-018-0056-x] [PMID: 30228301]
[4]
Nandy, S.B.; Lakshmanaswamy, R. Cancer stem cells and metastasis. Prog. Mol. Biol. Transl. Sci., 2017, 151, 137-176.
[http://dx.doi.org/10.1016/bs.pmbts.2017.07.007] [PMID: 29096892]
[5]
Sciacovelli, M.; Frezza, C. Metabolic reprogramming and epithelial-to-mesenchymal transition in cancer. FEBS J., 2017, 284(19), 3132-3144.
[http://dx.doi.org/10.1111/febs.14090] [PMID: 28444969]
[6]
El Hout, M.; Cosialls, E.; Mehrpour, M.; Hamaï, A. Crosstalk between autophagy and metabolic regulation of cancer stem cells. Mol. Cancer, 2020, 19(1), 27.
[http://dx.doi.org/10.1186/s12943-019-1126-8] [PMID: 32028963]
[7]
Li, L.; Bi, Z.; Wadgaonkar, P.; Lu, Y.; Zhang, Q.; Fu, Y.; Thakur, C.; Wang, L.; Chen, F. Metabolic and epigenetic reprogramming in the arsenic-induced cancer stem cells. Semin. Cancer Biol., 2019, 57, 10-18.
[http://dx.doi.org/10.1016/j.semcancer.2019.04.003] [PMID: 31009762]
[8]
Park, E.K.; Lee, J.C.; Park, J.W.; Bang, S.Y.; Yi, S.A.; Kim, B.K.; Park, J.H.; Kwon, S.H.; You, J.S.; Nam, S.W.; Cho, E.J.; Han, J.W. Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53. Cell Death Dis., 2015, 6(11), e1964.
[http://dx.doi.org/10.1038/cddis.2015.313] [PMID: 26539911]
[9]
Lee, S.Y.; Ju, M.K.; Jeon, H.M.; Lee, Y.J.; Kim, C.H.; Park, H.G.; Han, S.I.; Kang, H.S. Oncogenic metabolism acts as a prerequisite step for induction of cancer metastasis and cancer stem cell phenotype. Oxid. Med. Cell. Longev., 2018, 2018, 1027453.
[http://dx.doi.org/10.1155/2018/1027453] [PMID: 30671168]
[10]
Yi, M.; Li, J.; Chen, S.; Cai, J.; Ban, Y.; Peng, Q.; Zhou, Y.; Zeng, Z.; Peng, S.; Li, X.; Xiong, W.; Li, G.; Xiang, B. Emerging role of lipid metabolism alterations in Cancer stem cells. J. Exp. Clin. Cancer Res., 2018, 37(1), 118.
[http://dx.doi.org/10.1186/s13046-018-0784-5] [PMID: 29907133]
[11]
Zhao, G.; Cardenas, H.; Matei, D. Ovarian cancer-why lipids matter. Cancers (Basel), 2019, 11(12), 1870.
[http://dx.doi.org/10.3390/cancers11121870] [PMID: 31769430]
[12]
Pepino, M.Y.; Kuda, O.; Samovski, D.; Abumrad, N.A. Structure- function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu. Rev. Nutr., 2014, 34, 281-303.
[http://dx.doi.org/10.1146/annurev-nutr-071812-161220] [PMID: 24850384]
[13]
Jay, A.G.; Hamilton, J.A. The enigmatic membrane fatty acid transporter CD36: New insights into fatty acid binding and their effects on uptake of oxidized LDL. Prostaglandins Leukot. Essent. Fatty Acids, 2018, 138, 64-70.
[http://dx.doi.org/10.1016/j.plefa.2016.05.005] [PMID: 27288302]
[14]
Xu, W.H.; Qu, Y.Y.; Wang, J.; Wang, H.K.; Wan, F.N.; Zhao, J.Y.; Zhang, H.L.; Ye, D.W. Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients. J. Cancer, 2019, 10(19), 4522-4531.
[http://dx.doi.org/10.7150/jca.30989] [PMID: 31528216]
[15]
Nath, A.; Chan, C. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers. Sci. Rep., 2016, 6, 18669.
[http://dx.doi.org/10.1038/srep18669] [PMID: 26725848]
[16]
Ghoneum, A.; Gonzalez, D.; Abdulfattah, A.Y.; Said, N. Metabolic plasticity in ovarian cancer stem cells. Cancers (Basel), 2020, 12(5), 1267.
[http://dx.doi.org/10.3390/cancers12051267] [PMID: 32429566]
[17]
Hale, J.S.; Otvos, B.; Sinyuk, M.; Alvarado, A.G.; Hitomi, M.; Stoltz, K.; Wu, Q.; Flavahan, W.; Levison, B.; Johansen, M.L.; Schmitt, D.; Neltner, J.M.; Huang, P.; Ren, B.; Sloan, A.E.; Silverstein, R.L.; Gladson, C.L.; DiDonato, J.A.; Brown, J.M.; McIntyre, T.; Hazen, S.L.; Horbinski, C.; Rich, J.N.; Lathia, J.D. Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression. Stem Cells, 2014, 32(7), 1746-1758.
[http://dx.doi.org/10.1002/stem.1716] [PMID: 24737733]
[18]
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]
[19]
Sachs, K.; Sarver, A.L.; Noble-Orcutt, K.E.; LaRue, R.S.; Antony, M.L.; Chang, D.; Lee, Y.; Navis, C.M.; Hillesheim, A.L.; Nykaza, I.R.; Ha, N.A.; Hansen, C.J.; Karadag, F.K.; Bergerson, R.J.; Verneris, M.R.; Meredith, M.M.; Schomaker, M.L.; Linden, M.A.; Myers, C.L.; Largaespada, D.A.; Sachs, Z. Single-cell gene expression analyses reveal distinct self-renewing and proliferating subsets in the leukemia stem cell compartment in acute myeloid leukemia. Cancer Res., 2020, 80(3), 458-470.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2932] [PMID: 31784425]
[20]
Landberg, N.; von Palffy, S.; Askmyr, M.; Lilljebjörn, H.; Sandén, C.; Rissler, M.; Mustjoki, S.; Hjorth-Hansen, H.; Richter, J.; Ågerstam, H.; Järås, M.; Fioretos, T. CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting. Haematologica, 2018, 103(3), 447-455.
[http://dx.doi.org/10.3324/haematol.2017.169946] [PMID: 29284680]
[21]
McKillop, I.H.; Girardi, C.A.; Thompson, K.J. Role of fatty acid binding proteins (FABPs) in cancer development and progression. Cell. Signal., 2019, 62, 109336.
[http://dx.doi.org/10.1016/j.cellsig.2019.06.001] [PMID: 31170472]
[22]
Morihiro, Y.; Yasumoto, Y.; Vaidyan, L.K.; Sadahiro, H.; Uchida, T.; Inamura, A.; Sharifi, K.; Ideguchi, M.; Nomura, S.; Tokuda, N.; Kashiwabara, S.; Ishii, A.; Ikeda, E.; Owada, Y.; Suzuki, M. Fatty acid binding protein 7 as a marker of glioma stem cells. Pathol. Int., 2013, 63(11), 546-553.
[http://dx.doi.org/10.1111/pin.12109] [PMID: 24274717]
[23]
De Rosa, A.; Pellegatta, S.; Rossi, M.; Tunici, P.; Magnoni, L.; Speranza, M.C.; Malusa, F.; Miragliotta, V.; Mori, E.; Finocchiaro, G.; Bakker, A. A radial glia gene marker, fatty acid binding protein 7 (FABP7), is involved in proliferation and invasion of glioblastoma cells. PLoS One, 2012, 7(12), e52113.
[http://dx.doi.org/10.1371/journal.pone.0052113] [PMID: 23284888]
[24]
Ameer, F.; Scandiuzzi, L.; Hasnain, S.; Kalbacher, H.; Zaidi, N. De novo lipogenesis in health and disease. Metabolism, 2014, 63(7), 895-902.
[http://dx.doi.org/10.1016/j.metabol.2014.04.003] [PMID: 24814684]
[25]
Jafari, N.; Drury, J.; Morris, A.J.; Onono, F.O.; Stevens, P.D.; Gao, T.; Liu, J.; Wang, C.; Lee, E.Y.; Weiss, H.L.; Evers, B.M.; Zaytseva, Y.Y. De Novo fatty acid synthesis-driven sphingolipid metabolism promotes metastatic potential of colorectal cancer. Mol. Cancer Res., 2019, 17(1), 140-152.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0199] [PMID: 30154249]
[26]
Nickels, J.T., Jr New links between lipid accumulation and cancer progression. J. Biol. Chem., 2018, 293(17), 6635-6636.
[http://dx.doi.org/10.1074/jbc.H118.002654] [PMID: 29703762]
[27]
Swierczynski, J; Hebanowska, A; Sledzinski, T Role of abnormal lipid metabolism in development, progression, diagnosis, and therapy of pancreatic cancer. World J Gastroenterol., 2014, 20(9), 2279-2303.
[http://dx.doi.org/10.3748/wjg.v20.i9.2279]
[28]
Penfold, L.; Woods, A.; Muckett, P.; Nikitin, A.Y.; Kent, T.R.; Zhang, S.; Graham, R.; Pollard, A.; Carling, D. CAMKK2 promotes prostate cancer independently of AMPK via increased lipogenesis. Cancer Res., 2018, 78(24), 6747-6761.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-0585] [PMID: 30242113]
[29]
Li, G.; Li, M.; Hu, J.; Lei, R.; Xiong, H.; Ji, H.; Yin, H.; Wei, Q.; Hu, G. The microRNA-182-PDK4 axis regulates lung tumorigenesis by modulating pyruvate dehydrogenase and lipogenesis. Oncogene, 2017, 36(7), 989-998.
[http://dx.doi.org/10.1038/onc.2016.265] [PMID: 27641336]
[30]
Jones, S.F.; Infante, J.R. Molecular pathways: Fatty acid synthase. Clin. Cancer Res., 2015, 21(24), 5434-5438.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0126] [PMID: 26519059]
[31]
Pandey, P.R.; Xing, F.; Sharma, S.; Watabe, M.; Pai, S.K.; Iiizumi-Gairani, M.; Fukuda, K.; Hirota, S.; Mo, Y.Y.; Watabe, K. Elevated lipogenesis in epithelial stem-like cell confers survival advantage in ductal carcinoma in situ of breast cancer. Oncogene, 2013, 32(42), 5111-5122.
[http://dx.doi.org/10.1038/onc.2012.519] [PMID: 23208501]
[32]
Brandi, J.; Dando, I.; Pozza, E.D.; Biondani, G.; Jenkins, R.; Elliott, V.; Park, K.; Fanelli, G.; Zolla, L.; Costello, E.; Scarpa, A.; Cecconi, D.; Palmieri, M. Proteomic analysis of pancreatic cancer stem cells: Functional role of fatty acid synthesis and mevalonate pathways. J. Proteomics, 2017, 150, 310-322.
[http://dx.doi.org/10.1016/j.jprot.2016.10.002] [PMID: 27746256]
[33]
Yasumoto, Y.; Miyazaki, H.; Vaidyan, L.K.; Kagawa, Y.; Ebrahimi, M.; Yamamoto, Y.; Ogata, M.; Katsuyama, Y.; Sadahiro, H.; Suzuki, M.; Owada, Y. Inhibition of fatty acid synthase decreases expression of stemness markers in glioma stem cells. PLoS One, 2016, 11(1), e0147717.
[http://dx.doi.org/10.1371/journal.pone.0147717] [PMID: 26808816]
[34]
Pandey, P.R.; Okuda, H.; Watabe, M.; Pai, S.K.; Liu, W.; Kobayashi, A.; Xing, F.; Fukuda, K.; Hirota, S.; Sugai, T.; Wakabayashi, G.; Koeda, K.; Kashiwaba, M.; Suzuki, K.; Chiba, T.; Endo, M.; Fujioka, T.; Tanji, S.; Mo, Y.Y.; Cao, D.; Wilber, A.C.; Watabe, K. Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res. Treat., 2011, 130(2), 387-398.
[http://dx.doi.org/10.1007/s10549-010-1300-6] [PMID: 21188630]
[35]
Vazquez-Martin, A.; Corominas-Faja, B.; Cufi, S.; Vellon, L.; Oliveras-Ferraros, C.; Menendez, O.J.; Joven, J.; Lupu, R.; Menendez, J.A. The mitochondrial H(+)-ATP synthase and the lipogenic switch: new core components of metabolic reprogramming in induced pluripotent stem (iPS) cells. Cell Cycle, 2013, 12(2), 207-218.
[http://dx.doi.org/10.4161/cc.23352] [PMID: 23287468]
[36]
Schcolnik-Cabrera, A.; Chávez-Blanco, A.; Domínguez-Gómez, G.; Taja-Chayeb, L.; Morales-Barcenas, R.; Trejo-Becerril, C.; Perez-Cardenas, E.; Gonzalez-Fierro, A.; Dueñas-González, A. Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy. Expert Opin. Investig. Drugs, 2018, 27(5), 475-489.
[http://dx.doi.org/10.1080/13543784.2018.1471132] [PMID: 29723075]
[37]
Menendez, J.A.; Lupu, R. Fatty acid synthase (FASN) as a therapeutic target in breast cancer. Expert Opin. Ther. Targets, 2017, 21(11), 1001-1016.
[http://dx.doi.org/10.1080/14728222.2017.1381087] [PMID: 28922023]
[38]
DeBose-Boyd, R.A.; Ye, J. SREBPs in lipid metabolism, insulin signaling, and beyond. Trends Biochem. Sci., 2018, 43(5), 358-368.
[http://dx.doi.org/10.1016/j.tibs.2018.01.005] [PMID: 29500098]
[39]
Shimano, H.; Sato, R. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology. Nat. Rev. Endocrinol., 2017, 13(12), 710-730.
[http://dx.doi.org/10.1038/nrendo.2017.91] [PMID: 28849786]
[40]
Perone, Y.; Farrugia, A.J.; Rodríguez-Meira, A.; Győrffy, B.; Ion, C.; Uggetti, A.; Chronopoulos, A.; Marrazzo, P.; Faronato, M.; Shousha, S.; Davies, C.; Steel, J.H.; Patel, N.; Del Rio Hernandez, A.; Coombes, C.; Pruneri, G.; Lim, A.; Calvo, F.; Magnani, L. SREBP1 drives Keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer. Nat. Commun., 2019, 10(1), 2115.
[http://dx.doi.org/10.1038/s41467-019-09676-y] [PMID: 31073170]
[41]
Wen, Y.A.; Xiong, X.; Zaytseva, Y.Y.; Napier, D.L.; Vallee, E.; Li, A.T.; Wang, C.; Weiss, H.L.; Evers, B.M.; Gao, T. Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis., 2018, 9(3), 265.
[http://dx.doi.org/10.1038/s41419-018-0330-6] [PMID: 29449559]
[42]
Li, X.; Wu, J.B.; Li, Q.; Shigemura, K.; Chung, L.W.; Huang, W.C. SREBP-2 promotes stem cell-like properties and metastasis by transcriptional activation of c-Myc in prostate cancer. Oncotarget, 2016, 7(11), 12869-12884.
[http://dx.doi.org/10.18632/oncotarget.7331] [PMID: 26883200]
[43]
Peck, B.; Schulze, A. Lipid desaturation - the next step in targeting lipogenesis in cancer? FEBS J., 2016, 283(15), 2767-2778.
[http://dx.doi.org/10.1111/febs.13681] [PMID: 26881388]
[44]
Li, J.; Condello, S.; Thomes-Pepin, J.; Ma, X.; Xia, Y.; Hurley, T.D.; Matei, D.; Cheng, J.X. Lipid desaturation is a metabolic marker and therapeutic target of ovarian cancer stem cells. Cell Stem Cell, 2017, 20(3), 303-314.e5.
[http://dx.doi.org/10.1016/j.stem.2016.11.004] [PMID: 28041894]
[45]
Qin, X.Y.; Su, T.; Yu, W.; Kojima, S. Lipid desaturation-associated endoplasmic reticulum stress regulates MYCN gene expression in hepatocellular carcinoma cells. Cell Death Dis., 2020, 11(1), 66.
[http://dx.doi.org/10.1038/s41419-020-2257-y] [PMID: 31988297]
[46]
ALJohani, A.M.; Syed, D.N.; Ntambi, J.M. Insights into stearoyl-coa desaturase-1 regulation of systemic metabolism. Trends Endocrinol. Metab., 2017, 28(12), 831-842.
[http://dx.doi.org/10.1016/j.tem.2017.10.003] [PMID: 29089222]
[47]
Noto, A.; Raffa, S.; De Vitis, C.; Roscilli, G.; Malpicci, D.; Coluccia, P.; Di Napoli, A.; Ricci, A.; Giovagnoli, M.R.; Aurisicchio, L.; Torrisi, M.R.; Ciliberto, G.; Mancini, R. Stearoyl-CoA desaturase-1 is a key factor for lung cancer-initiating cells. Cell Death Dis., 2013, 4(12), e947.
[http://dx.doi.org/10.1038/cddis.2013.444] [PMID: 24309934]
[48]
Noto, A.; De Vitis, C.; Pisanu, M.E.; Roscilli, G.; Ricci, G.; Catizone, A.; Sorrentino, G.; Chianese, G.; Taglialatela-Scafati, O.; Trisciuoglio, D.; Del Bufalo, D.; Di Martile, M.; Di Napoli, A.; Ruco, L.; Costantini, S.; Jakopin, Z.; Budillon, A.; Melino, G.; Del Sal, G.; Ciliberto, G.; Mancini, R. Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ. Oncogene, 2017, 36(32), 4671-4672.
[http://dx.doi.org/10.1038/onc.2017.212] [PMID: 28628115]
[49]
Pisanu, M.E.; Noto, A.; De Vitis, C.; Morrone, S.; Scognamiglio, G.; Botti, G.; Venuta, F.; Diso, D.; Jakopin, Z.; Padula, F.; Ricci, A.; Mariotta, S.; Giovagnoli, M.R.; Giarnieri, E.; Amelio, I.; Agostini, M.; Melino, G.; Ciliberto, G.; Mancini, R. Blockade of Stearoyl-CoA-desaturase 1 activity reverts resistance to cisplatin in lung cancer stem cells. Cancer Lett., 2017, 406, 93-104.
[http://dx.doi.org/10.1016/j.canlet.2017.07.027] [PMID: 28797843]
[50]
Pisanu, M.E.; Maugeri-Saccà, M.; Fattore, L.; Bruschini, S.; De Vitis, C.; Tabbì, E.; Bellei, B.; Migliano, E.; Kovacs, D.; Camera, E.; Picardo, M.; Jakopin, Z.; Cippitelli, C.; Bartolazzi, A.; Raffa, S.; Torrisi, M.R.; Fulciniti, F.; Ascierto, P.A.; Ciliberto, G.; Mancini, R. Inhibition of stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF- mutated melanoma. J. Exp. Clin. Cancer Res., 2018, 37(1), 318.
[http://dx.doi.org/10.1186/s13046-018-0989-7] [PMID: 30558661]
[51]
Ma, X.L.; Sun, Y.F.; Wang, B.L.; Shen, M.N.; Zhou, Y.; Chen, J.W.; Hu, B.; Gong, Z.J.; Zhang, X.; Cao, Y.; Pan, B.S.; Zhou, J.; Fan, J.; Guo, W.; Yang, X.R. Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target. BMC Cancer, 2019, 19(1), 760.
[http://dx.doi.org/10.1186/s12885-019-5963-z] [PMID: 31370822]
[52]
Choi, S.; Yoo, Y.J.; Kim, H.; Lee, H.; Chung, H.; Nam, M.H.; Moon, J.Y.; Lee, H.S.; Yoon, S.; Kim, W.Y. Clinical and biochemical relevance of monounsaturated fatty acid metabolism targeting strategy for cancer stem cell elimination in colon cancer. Biochem. Biophys. Res. Commun., 2019, 519(1), 100-105.
[http://dx.doi.org/10.1016/j.bbrc.2019.08.137] [PMID: 31481234]
[53]
Vriens, K.; Christen, S.; Parik, S.; Broekaert, D.; Yoshinaga, K.; Talebi, A.; Dehairs, J.; Escalona-Noguero, C.; Schmieder, R.; Cornfield, T.; Charlton, C.; Romero-Pérez, L.; Rossi, M.; Rinaldi, G.; Orth, M.F.; Boon, R.; Kerstens, A.; Kwan, S.Y.; Faubert, B.; Méndez-Lucas, A.; Kopitz, C.C.; Chen, T.; Fernandez-Garcia, J.; Duarte, J.A.G.; Schmitz, A.A.; Steigemann, P.; Najimi, M.; Hägebarth, A.; Van Ginderachter, J.A.; Sokal, E.; Gotoh, N.; Wong, K.K.; Verfaillie, C.; Derua, R.; Munck, S.; Yuneva, M.; Beretta, L.; DeBerardinis, R.J.; Swinnen, J.V.; Hodson, L.; Cassiman, D.; Verslype, C.; Christian, S.; Grünewald, S.; Grünewald, T.G.P.; Fendt, S.M. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity. Nature, 2019, 566(7744), 403-406.
[http://dx.doi.org/10.1038/s41586-019-0904-1] [PMID: 30728499]
[54]
Walther, T.C.; Chung, J.; Farese, R.V., Jr Lipid droplet biogenesis. Annu. Rev. Cell Dev. Biol., 2017, 33, 491-510.
[http://dx.doi.org/10.1146/annurev-cellbio-100616-060608] [PMID: 28793795]
[55]
Olzmann, J.A.; Carvalho, P. Dynamics and functions of lipid droplets. Nat. Rev. Mol. Cell Biol., 2019, 20(3), 137-155.
[http://dx.doi.org/10.1038/s41580-018-0085-z] [PMID: 30523332]
[56]
Tirinato, L.; Pagliari, F.; Limongi, T.; Marini, M.; Falqui, A.; Seco, J.; Candeloro, P.; Liberale, C.; Di Fabrizio, E. An overview of lipid droplets in cancer and cancer stem cells. Stem Cells Int., 2017, 2017, 1656053.
[http://dx.doi.org/10.1155/2017/1656053] [PMID: 28883835]
[57]
Petan, T.; Jarc, E.; Jusović, M. Lipid droplets in cancer: guardians of fat in a stressful world. Molecules, 2018, 23(8), 1941.
[http://dx.doi.org/10.3390/molecules23081941] [PMID: 30081476]
[58]
Hershey, B.J.; Vazzana, R.; Joppi, D.L.; Havas, K.M. Lipid droplets define a sub-population of breast cancer stem cells. J. Clin. Med., 2019, 9(1), 87.
[http://dx.doi.org/10.3390/jcm9010087] [PMID: 31905780]
[59]
Tirinato, L.; Liberale, C.; Di Franco, S.; Candeloro, P.; Benfante, A.; La Rocca, R.; Potze, L.; Marotta, R.; Ruffilli, R.; Rajamanickam, V.P.; Malerba, M.; De Angelis, F.; Falqui, A.; Carbone, E.; Todaro, M.; Medema, J.P.; Stassi, G.; Di Fabrizio, E. Lipid droplets: a new player in colorectal cancer stem cells unveiled by spectroscopic imaging. Stem Cells, 2015, 33(1), 35-44.
[http://dx.doi.org/10.1002/stem.1837] [PMID: 25186497]
[60]
Giampietri, C.; Petrungaro, S.; Cordella, M.; Tabolacci, C.; Tomaipitinca, L.; Facchiano, A.; Eramo, A.; Filippini, A.; Facchiano, F.; Ziparo, E. Lipid Storage and autophagy in melanoma cancer cells. Int. J. Mol. Sci., 2017, 18(6), 1271.
[http://dx.doi.org/10.3390/ijms18061271] [PMID: 28617309]
[61]
Houten, S.M.; Violante, S.; Ventura, F.V.; Wanders, R.J. The biochemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders. Annu. Rev. Physiol., 2016, 78, 23-44.
[http://dx.doi.org/10.1146/annurev-physiol-021115-105045] [PMID: 26474213]
[62]
Ma, Y.; Temkin, S.M.; Hawkridge, A.M.; Guo, C.; Wang, W.; Wang, X.Y.; Fang, X. Fatty acid oxidation: An emerging facet of metabolic transformation in cancer. Cancer Lett., 2018, 435, 92-100.
[http://dx.doi.org/10.1016/j.canlet.2018.08.006] [PMID: 30102953]
[63]
Corbet, C.; Feron, O. Emerging roles of lipid metabolism in cancer progression. Curr. Opin. Clin. Nutr. Metab. Care, 2017, 20(4), 254-260.
[http://dx.doi.org/10.1097/MCO.0000000000000381] [PMID: 28403011]
[64]
Wang, C.; Shao, L.; Pan, C.; Ye, J.; Ding, Z.; Wu, J.; Du, Q.; Ren, Y.; Zhu, C. Elevated level of mitochondrial reactive oxygen species via fatty acid β-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition. Stem Cell Res. Ther., 2019, 10(1), 175.
[http://dx.doi.org/10.1186/s13287-019-1265-2] [PMID: 31196164]
[65]
Chen, C.L.; Uthaya Kumar, D.B.; Punj, V.; Xu, J.; Sher, L.; Tahara, S.M.; Hess, S.; Machida, K. NANOG metabolically reprograms tumor-initiating stem-like cells through tumorigenic changes in oxidative phosphorylation and fatty acid metabolism. Cell Metab., 2016, 23(1), 206-219.
[http://dx.doi.org/10.1016/j.cmet.2015.12.004] [PMID: 26724859]
[66]
Ito, K.; Carracedo, A.; Weiss, D.; Arai, F.; Ala, U.; Avigan, D.E.; Schafer, Z.T.; Evans, R.M.; Suda, T.; Lee, C.H.; Pandolfi, P.P. A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat. Med., 2012, 18(9), 1350-1358.
[http://dx.doi.org/10.1038/nm.2882] [PMID: 22902876]
[67]
Qu, Q.; Zeng, F.; Liu, X.; Wang, Q.J.; Deng, F. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. Cell Death Dis., 2016, 7(5), e2226.
[http://dx.doi.org/10.1038/cddis.2016.132] [PMID: 27195673]
[68]
Melone, M.A.B.; Valentino, A.; Margarucci, S.; Galderisi, U.; Giordano, A.; Peluso, G. The carnitine system and cancer metabolic plasticity. Cell Death Dis., 2018, 9(2), 228.
[http://dx.doi.org/10.1038/s41419-018-0313-7] [PMID: 29445084]
[69]
Shi, J.; Fu, H.; Jia, Z.; He, K.; Fu, L.; Wang, W. High Expression of CPT1A Predicts Adverse Outcomes: A Potential Therapeutic Target for Acute Myeloid Leukemia. EBioMedicine, 2016, 14, 55-64.
[http://dx.doi.org/10.1016/j.ebiom.2016.11.025] [PMID: 27916548]
[70]
Ricciardi, M.R.; Mirabilii, S.; Allegretti, M.; Licchetta, R.; Calarco, A.; Torrisi, M.R.; Foà, R.; Nicolai, R.; Peluso, G.; Tafuri, A. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood, 2015, 126(16), 1925-1929.
[http://dx.doi.org/10.1182/blood-2014-12-617498] [PMID: 26276667]
[71]
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]
[72]
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]
[73]
Shao, H.; Mohamed, E.M.; Xu, G.G.; Waters, M.; Jing, K.; Ma, Y.; Zhang, Y.; Spiegel, S.; Idowu, M.O.; Fang, X. Carnitine palmitoyltransferase 1A functions to repress FoxO transcription factors to allow cell cycle progression in ovarian cancer. Oncotarget, 2016, 7(4), 3832-3846.
[http://dx.doi.org/10.18632/oncotarget.6757] [PMID: 26716645]
[74]
Wang, Y.N.; Zeng, Z.L.; Lu, J.; Wang, Y.; Liu, Z.X.; He, M.M.; Zhao, Q.; Wang, Z.X.; Li, T.; Lu, Y.X.; Wu, Q.N.; Yu, K.; Wang, F.; Pu, H.Y.; Li, B.; Jia, W.H.; Shi, M.; Xie, D.; Kang, T.B.; Huang, P.; Ju, H.Q.; Xu, R.H. CPT1A-mediated fatty acid oxidation promotes colorectal cancer cell metastasis by inhibiting anoikis. Oncogene, 2018, 37(46), 6025-6040.
[http://dx.doi.org/10.1038/s41388-018-0384-z] [PMID: 29995871]
[75]
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]
[76]
Aiderus, A.; Black, M.A.; Dunbier, A.K. Fatty acid oxidation is associated with proliferation and prognosis in breast and other cancers. BMC Cancer, 2018, 18(1), 805.
[http://dx.doi.org/10.1186/s12885-018-4626-9] [PMID: 30092766]
[77]
Du, W.; Zhang, L.; Brett-Morris, A.; Aguila, B.; Kerner, J.; Hoppel, C.L.; Puchowicz, M.; Serra, D.; Herrero, L.; Rini, B.I.; Campbell, S.; Welford, S.M. HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism. Nat. Commun., 2017, 8(1), 1769.
[http://dx.doi.org/10.1038/s41467-017-01965-8] [PMID: 29176561]
[78]
Wang, T.; Fahrmann, J.F.; Lee, H.; Li, Y.J.; Tripathi, S.C.; Yue, C.; Zhang, C.; Lifshitz, V.; Song, J.; Yuan, Y.; Somlo, G.; Jandial, R.; Ann, D.; Hanash, S.; Jove, R.; Yu, H. JAK/STAT3-regulated fatty acid β-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab., 2018, 27(1), 136-150.e5.
[http://dx.doi.org/10.1016/j.cmet.2017.11.001] [PMID: 29249690]
[79]
Carvalho, M.A.; Zecchin, K.G.; Seguin, F.; Bastos, D.C.; Agostini, M.; Rangel, A.L.; Veiga, S.S.; Raposo, H.F.; Oliveira, H.C.; Loda, M.; Coletta, R.D.; Graner, E. Fatty acid synthase inhibition with Orlistat promotes apoptosis and reduces cell growth and lymph node metastasis in a mouse melanoma model. Int. J. Cancer, 2008, 123(11), 2557-2565.
[http://dx.doi.org/10.1002/ijc.23835] [PMID: 18770866]
[80]
Dowling, S.; Cox, J.; Cenedella, R.J. Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids, 2009, 44(6), 489-498.
[http://dx.doi.org/10.1007/s11745-009-3298-2] [PMID: 19381703]
[81]
Menendez, J.A.; Vellon, L.; Lupu, R. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann. Oncol., 2005, 16(8), 1253-1267.
[http://dx.doi.org/10.1093/annonc/mdi239] [PMID: 15870086]
[82]
Nagao, K.; Shinohara, N.; Smit, F.; de Weijert, M.; Jannink, S.; Owada, Y.; Mulders, P.; Oosterwijk, E.; Matsuyama, H. Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma. BMC Cancer, 2018, 18(1), 1114.
[http://dx.doi.org/10.1186/s12885-018-5060-8] [PMID: 30442117]
[83]
Li, X.; Chen, Y.T.; Hu, P.; Huang, W.C. Fatostatin displays high antitumor activity in prostate cancer by blocking SREBP-regulated metabolic pathways and androgen receptor signaling. Mol. Cancer Ther., 2014, 13(4), 855-866.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0797] [PMID: 24493696]
[84]
Siqingaowa, S.S.; Sekar, S.; Gopalakrishnan, V.; Taghibiglou, C. Sterol regulatory element-binding protein 1 inhibitors decrease pancreatic cancer cell viability and proliferation. Biochem. Biophys. Res. Commun., 2017, 488(1), 136-140.
[http://dx.doi.org/10.1016/j.bbrc.2017.05.023] [PMID: 28483521]
[85]
Gao, S.; Shi, Z.; Li, X.; Li, W.; Wang, Y.; Liu, Z.; Jiang, J. Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma. Oncol. Rep., 2018, 39(4), 1919-1929.
[http://dx.doi.org/10.3892/or.2018.6265] [PMID: 29436682]
[86]
Zhou, C.; Qian, W.; Ma, J.; Cheng, L.; Jiang, Z.; Yan, B.; Li, J.; Duan, W.; Sun, L.; Cao, J.; Wang, F.; Wu, E.; Wu, Z.; Ma, Q.; Li, X. Resveratrol enhances the chemotherapeutic response and reverses the stemness induced by gemcitabine in pancreatic cancer cells via targeting SREBP1. Cell Prolif., 2019, 52(1), e12514.
[http://dx.doi.org/10.1111/cpr.12514] [PMID: 30341797]
[87]
Tracz-Gaszewska, Z.; Dobrzyn, P. Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers (Basel), 2019, 11(7), 948.
[http://dx.doi.org/10.3390/cancers11070948] [PMID: 31284458]
[88]
Winterton, S.E.; Capota, E.; Wang, X.; Chen, H.; Mallipeddi, P.L.; Williams, N.S.; Posner, B.A.; Nijhawan, D.; Ready, J.M. Discovery of cytochrome P450 4F11 activated inhibitors of stearoyl coenzyme A desaturase. J. Med. Chem., 2018, 61(12), 5199-5221.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00052] [PMID: 29869888]
[89]
Theodoropoulos, P.C.; Gonzales, S.S.; Winterton, S.E.; Rodriguez-Navas, C.; McKnight, J.S.; Morlock, L.K.; Hanson, J.M.; Cross, B.; Owen, A.E.; Duan, Y.; Moreno, J.R.; Lemoff, A.; Mirzaei, H.; Posner, B.A.; Williams, N.S.; Ready, J.M.; Nijhawan, D. Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase. Nat. Chem. Biol., 2016, 12(4), 218-225.
[http://dx.doi.org/10.1038/nchembio.2016] [PMID: 26829472]
[90]
Cheng, S.; Wang, G.; Wang, Y.; Cai, L.; Qian, K.; Ju, L.; Liu, X.; Xiao, Y.; Wang, X. Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer. Clin. Sci. (Lond.), 2019, 133(15), 1745-1758.
[http://dx.doi.org/10.1042/CS20190587] [PMID: 31358595]
[91]
Yao, C.H.; Liu, G.Y.; Wang, R.; Moon, S.H.; Gross, R.W.; Patti, G.J. Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation. PLoS Biol., 2018, 16(3), e2003782.
[http://dx.doi.org/10.1371/journal.pbio.2003782] [PMID: 29596410]
[92]
Heuer, T.S.; Ventura, R.; Mordec, K.; Lai, J.; Fridlib, M.; Buckley, D.; Kemble, G. FASN inhibition and taxane treatment combine to enhance anti-tumor efficacy in diverse xenograft tumor models through disruption of tubulin palmitoylation and microtubule organization and FASN inhibition-mediated effects on oncogenic signaling and gene expression. EBioMedicine, 2017, 16, 51-62.
[http://dx.doi.org/10.1016/j.ebiom.2016.12.012] [PMID: 28159572]
[93]
Shen, M.; Tsai, Y.; Zhu, R.; Keng, P.C.; Chen, Y.; Chen, Y.; Lee, S.O. FASN-TGF-β1-PD-L1 axis contributes to the development of resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2018, 1863(3), 313-322.
[http://dx.doi.org/10.1016/j.bbalip.2017.12.012] [PMID: 29306075]
[94]
Liu, C.; Chikina, M.; Deshpande, R.; Menk, A.V.; Wang, T.; Tabib, T.; Brunazzi, E.A.; Vignali, K.M.; Sun, M.; Stolz, D.B.; Lafyatis, R.A.; Chen, W.; Delgoffe, G.M.; Workman, C.J.; Wendell, S.G.; Vignali, D.A.A. Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8+ T cell-derived interferon-γ. Immunity, 2019, 51(2), 381-397.e6.
[http://dx.doi.org/10.1016/j.immuni.2019.06.017] [PMID: 31350177]

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