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Frontiers of Medicine

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Front. Med.    2021, Vol. 15 Issue (5) : 679-692    https://doi.org/10.1007/s11684-021-0866-1
REVIEW
Potential of electron transfer and its application in dictating routes of biochemical processes associated with metabolic reprogramming
Ronghui Yang1,3, Guoguang Ying4,5,6(), Binghui Li1,2,3()
1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
2. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
3. Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University, Beijing 100069, China
4. Department of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
5. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China
6. National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
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Abstract

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
Keywords metabolic reprogramming      potential of electron transfer      cell proliferation      aerobic glycolysis      cancer metabolism     
Corresponding Author(s): Guoguang Ying,Binghui Li   
Just Accepted Date: 21 June 2021   Online First Date: 26 July 2021    Issue Date: 01 November 2021
 Cite this article:   
Ronghui Yang,Guoguang Ying,Binghui Li. Potential of electron transfer and its application in dictating routes of biochemical processes associated with metabolic reprogramming[J]. Front. Med., 2021, 15(5): 679-692.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0866-1
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I5/679
Fig.1  Electron transfer and energy generation in cells. (A) Model for electron transfer and ATP generation. Cellular metabolism releases electrons for electron transport chain (ETC) to generate ATP, and aerobic glycolysis produces ATP without the involvement of electrons. (B) Translocation of electrons. Electrons in NADH+ H+ or NADPH+ H+ could be translocated spatially or to each other. “–,” production of electrons; “+,” dissipation of electrons; red number, NADH+ H+; green number, NADPH+ H+; black number, NADH+ H+ or NADPH+ H+.
Metabolites Formula Y Y¯
Carbohydrate Glucose C6H12O6 24 4.00
Ribose C5H10O5 20 4.00
Fructose C6H12O6 24 4.00
Glyceraldehyde C3H6O3 12 4.00
Glyceric acid C3H6O4 10 3.33
Pyruvate C3H4O3 10 3.33
Lactate C3H6O3 12 4.00
Oxaloacetate C4H4O5 10 2.50
Malate C4H6O5 12 3.00
Fumarate C4H4O4 12 3.00
Succinate C4H6O4 14 3.50
α-Ketoglutarate C5H6O5 16 3.20
Citrate C6H8O7 18 3.00
Nucleobase Adenine C5H5N5 10 2.00
Guanine C5H5N5O 8 1.60
Cytosine C4H5N3O 10 2.50
Thymine C5H6N2O2 16 3.20
Uracil C4H4N2O2 10 2.50
Ribonucleoside Adenosine C10H13N5O4 30 3.00
Guanosine C10H13N5O5 28 2.80
Cytidine C9H13N3O5 30 3.33
Uridine C9H12N2O6 30 3.33
Deoxy-ribonucleoside Deoxyadenosine C10H13N5O3 32 3.20
Deoxyguanosine C10H13N5O4 30 3.00
Deoxycytidine C9H13N3O4 32 3.56
Deoxythymidine C10H14N2O5 38 3.80
Non-essential amino acids Glycine C2H5NO2 6 3.00
Serine C3H7NO3 10 3.33
Aspartate C4H7NO4 12 3.00
Asparagine C4H8N2O3 12 3.00
Glutamine C5H10N2O3 18 3.60
Glutamate C5H9NO4 18 3.60
Alanine C3H7NO2 12 4.00
Proline C5H9NO2 22 4.40
Semi-essential amino acids Histidine C6H9N3O2 20 3.33
Arginine C6H14N4O2 22 3.67
Essential amino acids Threonine C4H9NO3 16 4.00
Cysteinea C3H7NO2S 16 5.33
Methioninea C5H11NO2S 28 5.60
Lysine C6H14N2O2 28 4.66
Valine C5H11NO2 24 4.8
Leucine C6H13NO2 30 5.00
Isoleucine C6H13NO2 30 5.00
Tryptophan C11H12N2O2 46 4.18
Phenylalanine C9H11NO2 40 4.44
Tyrosine C9H11NO3 38 4.22
Acetyl-CoA Acetate C2H4O2 8 4.00
Lipid components Glycerol C3H8O3 14 4.67
Palmitate C16H32O2 92 5.75
Farnesolb C15H26O 84 5.60
End metabolites Carbon dioxide CO2 0
Water H2O 0
Urea/ammonia CH4N2O/NH3 0
Electron acceptor Oxygen O2 –4
Tab.1  The PET of metabolites
Pathways Initial substrates Final products ΔY
ATP generation Electrons+ 4H+ + O2 H2O ΔYETC<0
Glucose Pyruvate ΔYPyr-4,Glc = –4
Pyruvate CO2 ΔYCO2-20,Pyr = –20
Pyruvate Lactate ΔYLac+4,Pyr = +4
Citric acid cycle intermediates CO2 ΔYCAC-<0
Nucleotide biosynthesis Glucose Ribose+ CO2 ΔYoPPP Ribose-4, Glc= –4
Glucose Ribose ΔYnPPP Ribose_0, Glc= 0
Ribose+ amino acids Nucleotides ΔYNuc-<0
Sugar biosynthesis Glutamine Sugar ΔYSug-6,Gln = –6
Glucose Sugar ΔYSug 0,Glc = 0
Amino acid biosynthesis Glutamine Serine ΔYSer-8,Gln = –8
Glucose Serine ΔYSer-2,Glc = –2
Glutamine Alanine ΔYAla-6,Gln = –6
Glucose Alanine ΔYAla 0,Glc = 0
Glutamine Aspartate ΔYAsp-6,Gln = –6
Glucose Aspartate ΔYAsp 0,Glc = 0
Glutamine Proline ΔYPro+4,Gln = +4
Glucose Proline ΔYPro-2,Glc = –2
Lipid biosynthesis Glutamine Glycerol-3P ΔYGlo-4,Gln = –4
Glucose Glycerol-3P ΔYGlo+2,Glc = +2
Glutamine Palmitate+ Aspartate ΔY(Palm,Asp)+5.5,Gln = +5.5
Glutamine Palmitate+ Lactate ΔY(Palm,Lac)+5.5,Gln = +5.5
Glutamine Palmitate+ CO2 ΔY(Palm,CO2)-6.5,Gln = –6.5
Glucose Palmitate+ Aspartate ΔY(Palm,Asp)-0.5,Glc = –0.5
Glucose Palmitate+ Lactate ΔY(Palm,Lac)-0.5,Glc = –0.5
Glucose Palmitate+ CO2 ΔY(Palm,CO2)-12.5,Glc = –12.5
Tab.2  PET changes in metabolic transformations
Fig.2  Sugar metabolism. (A) Bacterial phosphoketolase pathway. Xylulose-5-phosphate/fructose-6-phosphate phosphoketolase (Xfp) catalyzes the production of acetyl phosphate (C2) from the breakdown of xylulose-5-phosphate (C5) or fructose-6-phosphate (C6). Glyceraldehydes-3-phosphate (C3) or erythrose-4-phosphate (C4) is simultaneously generated. (B) Glycolysis and pentose phosphate pathway (PPP). In the glycolytic pathway, glucose is converted to fructose-1,6-biphosphate (C6) that is further split by aldolase into dihydroxyacetone phosphate (C3) and glyceraldehydes-3-phosphate (C3). In PPP, glyceraldehydes-3-phosphate (C3), erythrose-4-phosphate (C4), xylulose-5-phosphate (C5), ribose-5-phosphate (C5), fructose-6-phosphate (C6), and sedoheptulose-7-phosphate are produced by transketolase or transaldolase.
Nutrients Products ΔY ΔYAc,Nutr ΔYGMR
Acetate Ac-CoA 0 0 +7.5
Leucine 3Ac-CoA –6 –2 +5.5
Glucose 2Ac-CoA –8 –4 +3.5
Lactate Ac-CoA –4 –4 +3.5
Alanine Ac-CoA –4 –4 +3.5
Aspartate Ac-CoA –4 –4 +3.5
Tyrosine 3Ac-CoA –14 –4.67 +2.83
Phenylalanine 3Ac-CoA –16 –5.33 +2.17
Tryptophan 3Ac-CoA+Formyl-THF –18 –6 +1.5
Lysine 2Ac-CoA –12 –6 +1.5
Isoleucine 2Ac-CoA –14 –7 +0.5
Tab.3  Metabolic equivalent of nutrients
Fig.3  Aerobic glycolysis results from energy requirement and electron balance. (A) In non-proliferating cells, anabolism is inactive and glucose is mainly oxidized to carbon dioxide through glycolysis and the citric acid cycle. Glucose catabolism produces electrons for mitochondrial ATP generation. (B) In proliferating cells, anabolism is active and produces electrons that could enter the mitochondria. By contrast, glucose is fermented to lactate to avoid electron production. Er, ATP generation from mitochondrial ETC; Eg, ATP generation from glycolysis; ΔE, additional ATP required for anabolic transformations.
1 JS Flier, MM Mueckler, P Usher, HF Lodish. Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 1987; 235(4795): 1492–1495
https://doi.org/10.1126/science.3103217 pmid: 3103217
2 DR Wise, RJ DeBerardinis, A Mancuso, N Sayed, XY Zhang, HK Pfeiffer, I Nissim, E Daikhin, M Yudkoff, SB McMahon, CB Thompson. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 2008; 105(48): 18782–18787
https://doi.org/10.1073/pnas.0810199105 pmid: 19033189
3 DR Wise, CB Thompson. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci 2010; 35(8): 427–433
https://doi.org/10.1016/j.tibs.2010.05.003 pmid: 20570523
4 C Sun, T Li, X Song, L Huang, Q Zang, J Xu, N Bi, G Jiao, Y Hao, Y Chen, R Zhang, Z Luo, X Li, L Wang, Z Wang, Y Song, J He, Z Abliz. Spatially resolved metabolomics to discover tumor-associated metabolic alterations. Proc Natl Acad Sci USA 2019; 116(1): 52–57
https://doi.org/10.1073/pnas.1808950116 pmid: 30559182
5 M Jain, R Nilsson, S Sharma, N Madhusudhan, T Kitami, AL Souza, R Kafri, MW Kirschner, CB Clish, VK Mootha. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 2012; 336(6084): 1040–1044
https://doi.org/10.1126/science.1218595 pmid: 22628656
6 J Zhu, CB Thompson. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol 2019; 20(7): 436–450
https://doi.org/10.1038/s41580-019-0123-5 pmid: 30976106
7 D Huang, C Li, H Zhang. Hypoxia and cancer cell metabolism. Acta Biochim Biophys Sin (Shanghai) 2014; 46(3): 214–219
https://doi.org/10.1093/abbs/gmt148 pmid: 24389642
8 O Warburg. On the origin of cancer cells. Science 1956; 123(3191): 309–314
https://doi.org/10.1126/science.123.3191.309 pmid: 13298683
9 CM Sousa, DE Biancur, X Wang, CJ Halbrook, MH Sherman, L Zhang, D Kremer, RF Hwang, AK Witkiewicz, H Ying, JM Asara, RM Evans, LC Cantley, CA Lyssiotis, AC Kimmelman. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature 2016; 536(7617): 479–483
https://doi.org/10.1038/nature19084 pmid: 27509858
10 JR Mayers, C Wu, CB Clish, P Kraft, ME Torrence, BP Fiske, C Yuan, Y Bao, MK Townsend, SS Tworoger, SM Davidson, T Papagiannakopoulos, A Yang, TL Dayton, S Ogino, MJ Stampfer, EL Giovannucci, ZR Qian, DA Rubinson, J Ma, HD Sesso, JM Gaziano, BB Cochrane, S Liu, J Wactawski-Wende, JE Manson, MN Pollak, AC Kimmelman, A Souza, K Pierce, TJ Wang, RE Gerszten, CS Fuchs, MG Vander Heiden, BM Wolpin. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 2014; 20(10): 1193–1198
https://doi.org/10.1038/nm.3686 pmid: 25261994
11 M Tönjes, S Barbus, YJ Park, W Wang, M Schlotter, AM Lindroth, SV Pleier, AHC Bai, D Karra, RM Piro, J Felsberg, A Addington, D Lemke, I Weibrecht, V Hovestadt, CG Rolli, B Campos, S Turcan, D Sturm, H Witt, TA Chan, C Herold-Mende, R Kemkemer, R König, K Schmidt, WE Hull, SM Pfister, M Jugold, SM Hutson, C Plass, JG Okun, G Reifenberger, P Lichter, B Radlwimmer. BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1. Nat Med 2013; 19(7): 901–908
https://doi.org/10.1038/nm.3217 pmid: 23793099
12 F Loayza-Puch, K Rooijers, LC Buil, J Zijlstra, JF Oude Vrielink, R Lopes, AP Ugalde, P van Breugel, I Hofland, J Wesseling, O van Tellingen, A Bex, R Agami. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading. Nature 2016; 530(7591): 490–494
https://doi.org/10.1038/nature16982 pmid: 26878238
13 W Liu, A Le, C Hancock, AN Lane, CV Dang, TW Fan, JM Phang. Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci USA 2012; 109(23): 8983–8988
https://doi.org/10.1073/pnas.1203244109 pmid: 22615405
14 KER Hollinshead, H Munford, KL Eales, C Bardella, C Li, C Escribano-Gonzalez, A Thakker, Y Nonnenmacher, K Kluckova, M Jeeves, R Murren, F Cuozzo, D Ye, G Laurenti, W Zhu, K Hiller, DJ Hodson, W Hua, IP Tomlinson, C Ludwig, Y Mao, DA Tennant. Oncogenic IDH1 mutations promote enhanced proline synthesis through PYCR1 to support the maintenance of mitochondrial redox homeostasis. Cell Rep 2018; 22(12): 3107–3114
https://doi.org/10.1016/j.celrep.2018.02.084 pmid: 29562167
15 AR Mullen, WW Wheaton, ES Jin, PH Chen, LB Sullivan, T Cheng, Y Yang, WM Linehan, NS Chandel, RJ DeBerardinis. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2012; 481(7381): 385–388
https://doi.org/10.1038/nature10642 pmid: 22101431
16 CM Metallo, PA Gameiro, EL Bell, KR Mattaini, J Yang, K Hiller, CM Jewell, ZR Johnson, DJ Irvine, L Guarente, JK Kelleher, MG Vander Heiden, O Iliopoulos, G Stephanopoulos. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012; 481(7381): 380–384
https://doi.org/10.1038/nature10602 pmid: 22101433
17 DR Wise, PS Ward, JE Shay, JR Cross, JJ Gruber, UM Sachdeva, JM Platt, RG DeMatteo, MC Simon, CB Thompson. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci USA 2011; 108(49): 19611–19616
https://doi.org/10.1073/pnas.1117773108 pmid: 22106302
18 Y Wang, C Bai, Y Ruan, M Liu, Q Chu, L Qiu, C Yang, B Li. Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia. Nat Commun 2019; 10(1): 201
https://doi.org/10.1038/s41467-018-08033-9 pmid: 30643150
19 X Gao, SH Lin, F Ren, JT Li, JJ Chen, CB Yao, HB Yang, SX Jiang, GQ Yan, D Wang, Y Wang, Y Liu, Z Cai, YY Xu, J Chen, W Yu, PY Yang, QY Lei. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nat Commun 2016; 7(1): 11960
https://doi.org/10.1038/ncomms11960 pmid: 27357947
20 ZT Schug, J Vande Voorde, E Gottlieb. The metabolic fate of acetate in cancer. Nat Rev Cancer 2016; 16(11): 708–717
https://doi.org/10.1038/nrc.2016.87 pmid: 27562461
21 ZT Schug, B Peck, DT Jones, Q Zhang, S Grosskurth, IS Alam, LM Goodwin, E Smethurst, S Mason, K Blyth, L McGarry, D James, E Shanks, G Kalna, RE Saunders, M Jiang, M Howell, F Lassailly, MZ Thin, B Spencer-Dene, G Stamp, NJ van den Broek, G Mackay, V Bulusu, JJ Kamphorst, S Tardito, D Strachan, AL Harris, EO Aboagye, SE Critchlow, MJ Wakelam, A Schulze, E Gottlieb. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell 2015; 27(1): 57–71
https://doi.org/10.1016/j.ccell.2014.12.002 pmid: 25584894
22 JJ Kamphorst, MK Chung, J Fan, JD Rabinowitz. Quantitative analysis of acetyl-CoA production in hypoxic cancer cells reveals substantial contribution from acetate. Cancer Metab 2014; 2(1): 23
https://doi.org/10.1186/2049-3002-2-23 pmid: 25671109
23 SA Comerford, Z Huang, X Du, Y Wang, L Cai, AK Witkiewicz, H Walters, MN Tantawy, A Fu, HC Manning, JD Horton, RE Hammer, SL McKnight, BP Tu. Acetate dependence of tumors. Cell 2014; 159(7): 1591–1602
https://doi.org/10.1016/j.cell.2014.11.020 pmid: 25525877
24 LK Boroughs, RJ DeBerardinis. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol 2015; 17(4): 351–359
https://doi.org/10.1038/ncb3124 pmid: 25774832
25 NN Pavlova, CB Thompson. The emerging hallmarks of cancer metabolism. Cell Metab 2016; 23(1): 27–47
https://doi.org/10.1016/j.cmet.2015.12.006 pmid: 26771115
26 A Vazquez, JJ Kamphorst, EK Markert, ZT Schug, S Tardito, E Gottlieb. Cancer metabolism at a glance. J Cell Sci 2016; 129(18): 3367–3373
https://doi.org/10.1242/jcs.181016 pmid: 27635066
27 M Liu, Y Wang, C Yang, Y Ruan, C Bai, Q Chu, Y Cui, C Chen, G Ying, B Li. Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth. J Exp Med 2020; 217(3): e20191226
https://doi.org/10.1084/jem.20191226 pmid: 31961917
28 B Alberts, A Johnson, J Lewis, M Raff, K Roberts, P Walter. Molecular Biology of the Cell. 5th edition. New York: Garland Science, 2008
29 DV Titov, V Cracan, RP Goodman, J Peng, Z Grabarek, VK Mootha. Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science 2016; 352(6282): 231–235
https://doi.org/10.1126/science.aad4017 pmid: 27124460
30 LB Sullivan, DY Gui, AM Hosios, LN Bush, E Freinkman, MG Vander Heiden. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 2015; 162(3): 552–563
https://doi.org/10.1016/j.cell.2015.07.017 pmid: 26232225
31 K Birsoy, T Wang, WW Chen, E Freinkman, M Abu-Remaileh, DM Sabatini. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 2015; 162(3): 540–551
https://doi.org/10.1016/j.cell.2015.07.016 pmid: 26232224
32 AR Mullen, Z Hu, X Shi, L Jiang, LK Boroughs, Z Kovacs, R Boriack, D Rakheja, LB Sullivan, WM Linehan, NS Chandel, RJ DeBerardinis. Oxidation of α-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects. Cell Rep 2014; 7(5): 1679–1690
https://doi.org/10.1016/j.celrep.2014.04.037 pmid: 24857658
33 M Li, Y Lu, Y Li, L Tong, XC Gu, J Meng, Y Zhu, L Wu, M Feng, N Tian, P Zhang, T Xu, SH Lin, X Tong. Transketolase deficiency protects the liver from DNA damage by increasing levels of ribose 5-phosphate and nucleotides. Cancer Res 2019; 79(14): 3689–3701
https://doi.org/10.1158/0008-5472.CAN-18-3776 pmid: 31101762
34 Q Li, T Qin, Z Bi, H Hong, L Ding, J Chen, W Wu, X Lin, W Fu, F Zheng, Y Yao, ML Luo, PE Saw, GM Wulf, X Xu, E Song, H Yao, H Hu. Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer. Nat Commun 2020; 11(1): 1456
https://doi.org/10.1038/s41467-020-15308-7 pmid: 32193458
35 CF Labuschagne, NJ van den Broek, GM Mackay, KH Vousden, OD Maddocks. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep 2014; 7(4): 1248–1258
https://doi.org/10.1016/j.celrep.2014.04.045 pmid: 24813884
36 OD Maddocks, CR Berkers, SM Mason, L Zheng, K Blyth, E Gottlieb, KH Vousden. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 2013; 493(7433): 542–546
https://doi.org/10.1038/nature11743 pmid: 23242140
37 SP Gravel, L Hulea, N Toban, E Birman, MJ Blouin, M Zakikhani, Y Zhao, I Topisirovic, J St-Pierre, M Pollak. Serine deprivation enhances antineoplastic activity of biguanides. Cancer Res 2014; 74(24): 7521–7533
https://doi.org/10.1158/0008-5472.CAN-14-2643-T pmid: 25377470
38 ODK Maddocks, D Athineos, EC Cheung, P Lee, T Zhang, NJF van den Broek, GM Mackay, CF Labuschagne, D Gay, F Kruiswijk, J Blagih, DF Vincent, KJ Campbell, F Ceteci, OJ Sansom, K Blyth, KH Vousden. Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature 2017; 544(7650): 372–376
https://doi.org/10.1038/nature22056 pmid: 28425994
39 L Yang, JC Garcia Canaveras, Z Chen, L Wang, L Liang, C Jang, JA Mayr, Z Zhang, JM Ghergurovich, L Zhan, S Joshi, Z Hu, MR McReynolds, X Su, E White, RJ Morscher, JD Rabinowitz. Serine catabolism feeds NADH when respiration is impaired. Cell Metab 2020; 31(4): 809–821.e6
https://doi.org/10.1016/j.cmet.2020.02.017 pmid: 32187526
40 MV Liberti, JW Locasale. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 2016; 41(3): 211–218
https://doi.org/10.1016/j.tibs.2015.12.001 pmid: 26778478
41 DG Kilburn, MD Lilly, FC Webb. The energetics of mammalian cell growth. J Cell Sci 1969; 4(3): 645–654
https://doi.org/10.1242/jcs.4.3.645 pmid: 5817088
42 N Slavov, BA Budnik, D Schwab, EM Airoldi, A van Oudenaarden. Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis. Cell Rep 2014; 7(3): 705–714
https://doi.org/10.1016/j.celrep.2014.03.057 pmid: 24767987
43 A Luengo, Z Li, DY Gui, LB Sullivan, M Zagorulya, BT Do, R Ferreira, A Naamati, A Ali, CA Lewis, CJ Thomas, S Spranger, NJ Matheson, MG Vander Heiden. Increased demand for NAD+ relative to ATP drives aerobic glycolysis. Mol Cell 2021; 81(4): 691–707.e6
https://doi.org/10.1016/j.molcel.2020.12.012 pmid: 33382985
44 T Epstein, L Xu, RJ Gillies, RA Gatenby. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane. Cancer Metab 2014; 2(1): 7
https://doi.org/10.1186/2049-3002-2-7 pmid: 24982758
45 Z Dai, AA Shestov, L Lai, JW Locasale. A flux balance of glucose metabolism clarifies the requirements of the Warburg effect. Biophys J 2016; 111(5): 1088–1100
https://doi.org/10.1016/j.bpj.2016.07.028 pmid: 27602736
46 M Shuler, F Kargi, M DeLisa. Bioprocess Engineering: Basic Concepts. 3rd edition. Upper Saddle River, NJ: Prentice Hall, 2017
47 JM Phang, W Liu, C Hancock, KJ Christian. The proline regulatory axis and cancer. Front Oncol 2012; 2: 60
https://doi.org/10.3389/fonc.2012.00060 pmid: 22737668
48 JM Berg, JL Tymoczko, L Stryer. Biochemistry. 7th edition. New York: W.H. Freeman, 2012
49 K Glenn, KS Smith. Allosteric regulation of Lactobacillus plantarum xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp). J Bacteriol 2015; 197(7): 1157–1163
https://doi.org/10.1128/JB.02380-14 pmid: 25605308
50 L Tirinato, F Pagliari, T Limongi, M Marini, A Falqui, J Seco, P Candeloro, C Liberale, E Di Fabrizio. An overview of lipid droplets in cancer and cancer stem cells. Stem Cells Int 2017; 2017: 1656053
https://doi.org/10.1155/2017/1656053 pmid: 28883835
51 Q Liu, Q Luo, A Halim, G Song. Targeting lipid metabolism of cancer cells: a promising therapeutic strategy for cancer. Cancer Lett 2017; 401: 39–45
https://doi.org/10.1016/j.canlet.2017.05.002 pmid: 28527945
52 G Medes, A Thomas, S Weinhouse. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res 1953; 13(1): 27–29
pmid: 13032945
53 M Ookhtens, R Kannan, I Lyon, N Baker. Liver and adipose tissue contributions to newly formed fatty acids in an ascites tumor. Am J Physiol 1984; 247(1 Pt 2): R146–R153
pmid: 6742224
54 S Balaban, ZD Nassar, AY Zhang, E Hosseini-Beheshti, MM Centenera, M Schreuder, HM Lin, A Aishah, B Varney, F Liu-Fu, LS Lee, SR Nagarajan, RF Shearer, RA Hardie, NL Raftopulos, MS Kakani, DN Saunders, J Holst, LG Horvath, LM Butler, AJ Hoy. Extracellular fatty acids are the major contributor to lipid synthesis in prostate cancer. Mol Cancer Res 2019; 17(4): 949–962
https://doi.org/10.1158/1541-7786.MCR-18-0347 pmid: 30647103
55 J Garcia-Bermudez, L Baudrier, EC Bayraktar, Y Shen, K La, R Guarecuco, B Yucel, D Fiore, B Tavora, E Freinkman, SH Chan, C Lewis, W Min, G Inghirami, DM Sabatini, K Birsoy. Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death. Nature 2019; 567(7746): 118–122
https://doi.org/10.1038/s41586-019-0945-5 pmid: 30760928
56 W Palm, CB Thompson. Nutrient acquisition strategies of mammalian cells. Nature 2017; 546(7657): 234–242
https://doi.org/10.1038/nature22379 pmid: 28593971
57 ZT Schafer, AR Grassian, L Song, Z Jiang, Z Gerhart-Hines, HY Irie, S Gao, P Puigserver, JS Brugge. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009; 461(7260): 109–113
https://doi.org/10.1038/nature08268 pmid: 19693011
58 CL Buchheit, KJ Weigel, ZT Schafer. Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression. Nat Rev Cancer 2014; 14(9): 632–641
https://doi.org/10.1038/nrc3789 pmid: 25098270
59 CK Lee, SH Jeong, C Jang, H Bae, YH Kim, I Park, SK Kim, GY Koh. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science 2019; 363(6427): 644–649
https://doi.org/10.1126/science.aav0173 pmid: 30733421
60 S Ganapathy-Kanniappan, JF Geschwind. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 2013; 12(1): 152
https://doi.org/10.1186/1476-4598-12-152 pmid: 24298908
61 WH Koppenol, PL Bounds, CV Dang. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11(5): 325–337
https://doi.org/10.1038/nrc3038 pmid: 21508971
62 G Hatzivassiliou, F Zhao, DE Bauer, C Andreadis, AN Shaw, D Dhanak, SR Hingorani, DA Tuveson, CB Thompson. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 2005; 8(4): 311–321
https://doi.org/10.1016/j.ccr.2005.09.008 pmid: 16226706
63 RU Svensson, SJ Parker, LJ Eichner, MJ Kolar, M Wallace, SN Brun, PS Lombardo, JL Van Nostrand, A Hutchins, L Vera, L Gerken, J Greenwood, S Bhat, G Harriman, WF Westlin, HJ Harwood Jr, A Saghatelian, R Kapeller, CM Metallo, RJ Shaw. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med 2016; 22(10): 1108–1119
https://doi.org/10.1038/nm.4181 pmid: 27643638
64 JE Stine, H Guo, X Sheng, X Han, MN Schointuch, TP Gilliam, PA Gehrig, C Zhou, VL Bae-Jump. The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti-tumorigenic effects in ovarian cancer. Oncotarget 2016; 7(1): 946–960
https://doi.org/10.18632/oncotarget.5834 pmid: 26503475
65 UE Martinez-Outschoorn, M Peiris-Pages, RG Pestell, F Sotgia, MP Lisanti. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol 2017; 14(1): 11–31
pmid: 27141887
66 JR Doherty, JL Cleveland. Targeting lactate metabolism for cancer therapeutics. J Clin Invest 2013; 123(9): 3685–3692
https://doi.org/10.1172/JCI69741 pmid: 23999443
67 RC Sun, NC Denko. Hypoxic regulation of glutamine metabolism through HIF1 and SIAH2 supports lipid synthesis that is necessary for tumor growth. Cell Metab 2014; 19(2): 285–292
https://doi.org/10.1016/j.cmet.2013.11.022 pmid: 24506869
68 JW Kim, I Tchernyshyov, GL Semenza, CV Dang. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3(3): 177–185
https://doi.org/10.1016/j.cmet.2006.02.002 pmid: 16517405
69 SK Shukla, V Purohit, K Mehla, V Gunda, NV Chaika, E Vernucci, RJ King, J Abrego, GD Goode, A Dasgupta, AL Illies, T Gebregiworgis, B Dai, JJ Augustine, D Murthy, KS Attri, O Mashadova, PM Grandgenett, R Powers, QP Ly, AJ Lazenby, JL Grem, F Yu, JM Matés, JM Asara, JW Kim, JH Hankins, C Weekes, MA Hollingsworth, NJ Serkova, AR Sasson, JB Fleming, JM Oliveto, CA Lyssiotis, LC Cantley, L Berim, PK Singh. MUC1 and HIF-1α signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell 2017; 32(1): 71–87.e7
https://doi.org/10.1016/j.ccell.2017.06.004 pmid: 28697344
70 E Furuta, SK Pai, R Zhan, S Bandyopadhyay, M Watabe, YY Mo, S Hirota, S Hosobe, T Tsukada, K Miura, S Kamada, K Saito, M Iiizumi, W Liu, J Ericsson, K Watabe. Fatty acid synthase gene is up-regulated by hypoxia via activation of Akt and sterol regulatory element binding protein-1. Cancer Res 2008; 68(4): 1003–1011
https://doi.org/10.1158/0008-5472.CAN-07-2489 pmid: 18281474
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