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摘要: 细胞能量异常是肿瘤细胞的十大特征之一,正常细胞能量代谢主要通过线粒体氧化磷酸化释放二氧化碳,而肿瘤细胞能量代谢主要通过有氧糖酵解产生乳酸代替二氧化碳释放,这种能量代谢的特点使内环境中二氧化碳释放减少。因此,肿瘤细胞处于一种低碳生活状态,具有体细胞逐渐恶变的进程中获得特征性生长表型,在肿瘤细胞增殖、侵袭转移中发挥独特的生物学作用。本文就肿瘤细胞低碳生活与肿瘤细胞主要的特殊能量需求、基因突变、环境选择、酸抵抗、凋亡逃避和肿瘤干细胞特性维持等机制进行综述。Abstract: The deregulation of cellular energetics is one of the hallmarks of cancer cells. The metabolism of tumor cells is unique in that aerobic glycolysis occurs with increased glycolysis and decreased mitochondrial oxidative phosphorylation, even in the presence of oxygen. The Warburg effect is related to the original observation that proliferating tumor cells consume glucose at a high rate and release lactate, not CO2. In terms of carbon emissions, a low carbon lifestyle exists in tumor cells. This lifestyle represents one such mechanism whereby increased entry of glucose ensures rapid proliferation and sustenance of biological processes critical for proliferation, metastasis, and adaptation, and further proliferation at the metastatic site. The underlying mechanisms involve directing glucose toward biosynthesis, rapid cell energy generation, gene mutation, environmental selection, acid resistance, escape from apoptosis and maintaince of tumor stem cell.
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Key words:
- glycolysis /
- tumor cell /
- low carbon
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[1] Martinez-Outschoorn UE, Lin Z, Ko YH, et al. Understanding the metabolic basis of drug resistance: therapeutic induction of the Warburg effect kills cancer cells[J]. Cell Cycle, 2011, 10(15):2521-2528. http://europepmc.org/articles/PMC3180190/ [2] Jiang P, Du W, Wang X, et al. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase[J]. Nat Cell Biol, 2011, 13(3):310-316. http://www.nature.com/articles/ncb2172 [3] Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways[J]. Science, 2001, 292 (5516):504-507. http://europepmc.org/abstract/MED/11283355 [4] Lee HC, Wei YH. Mitochondrial DNA instability and metabolic shift in human cancers[J]. Int J Mol Sci, 2009, 10(2):674-701. http://pubmedcentralcanada.ca/pmcc/articles/PMC2660656/ [5] López-Ríos F, Sánchez-Aragó M, García-García E, et al. Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas[J]. Cancer Res, 2007, 67(19):9013-9017. http://europepmc.org/abstract/MED/17909002 [6] Pollard PJ, Brière JJ, Alam NA, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations[J]. Hum Mol Genet, 2005, 14(15):2231-2239. http://jmg.bmj.com/lookup/external-ref?access_num=10.1093/hmg/ddi227&link_type=DOI [7] Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities[J]. Clin Cancer Res, 2009, 15 (21):6479-6483. http://www.tandfonline.com/servlet/linkout?suffix=CIT0024&dbid=8&doi=10.1586%2Fera.13.57&key=19861459 [8] Matoba S, Kang JG, Patino WD, et al. p53 regulates mitochondrial respiration[J]. Science, 2006, 312(5780):1650-1653. http://www.biomedcentral.com/pubmed/16728594 [9] Zhang C, Liu J, Liang Y, et al. Tumour-associated mutant p53 drives the Warburg effect[J]. Nat Commun, 2013, 4:2935. http://europepmc.org/articles/pmc3969270/ [10] Feron O. Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells[J]. Radiother Oncol, 2009, 92(3):329-333. http://so.med.wanfangdata.com.cn/ViewHTML/PeriodicalPaper_JJ0216094014.aspx [11] Zhang H, Gao P, Fukuda R, et al. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity[J]. Cancer Cell, 2007, 11(5): 407-420. http://europepmc.org/abstract/MED/17482131 [12] Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer[J]. Cancer Res, 2011, 71(22):6921-6925. http://carcin.oxfordjournals.org/cgi/ijlink?linkType=ABST&journalCode=canres&resid=71/22/6921 [13] Choi SY, Collins CC, Gout PW, et al. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite[J]? J Pathol, 2013, 230(4):350-355. http://www.ncbi.nlm.nih.gov/pubmed/23729358 [14] Sonveaux P, Végran F, Schroeder T, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice[J]. J Clin Invest, 2008, 118(12):3930-3942. http://pubmedcentralcanada.ca/pmcc/articles/PMC2582933/ [15] Bender T, Martinou JC. Where killers meet-permeabilization of the outer mitochondrial membrane during apoptosis[J]. Cold Spring Harb Perspect Biol, 2013, 5(1):a011106. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579398/ [16] Pradelli LA, Bénéteau M, Chauvin C, et al. Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation[J]. Oncogene, 2010, 29(11):1641-1652. http://www.ncbi.nlm.nih.gov/pubmed/19966861?access_num=19966861&link_type=MED [17] Chiche J, Rouleau M, Gounon P, et al. Hypoxic enlarged mitochondria protect cancer cells from apoptotic stimuli[J]. J Cell Physiol, 2010, 222(3):648-657. doi: 10.1002/jcp.21984 [18] Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate[J]. Cancer Cell, 2012, 21(3): 297-308. http://europepmc.org/abstract/MED/22439925 [19] Moon JS, Kim HE, Koh E, et al. Krüppel-like factor 4 (KLF4) activates the transcription of the gene for the platelet isoform of phosphofructokinase (PFKP) in breast cancer[J]. J Biol Chem, 2011, 286 (27):23808-23816. http://www.ncbi.nlm.nih.gov/pubmed/21586797 [20] Sun Q, Chen X, Ma J, et al. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth[J]. Proc Natl Acad Sci U S A, 2011, 108(10):4129-4134. http://www.researchgate.net/publication/235924487_Mammalian_target_of_rapamycin_up-regulation_of_pyruvate_kinase_isoenzyme_type_M2_is_critical_for_aerobic_glycolysis_and_tumor_growth
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