Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.
Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.
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DOI：
10.3390/ijms231710037
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发表时间：
2022-09-02
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
有氧糖酵解是许多人类癌症的新标志，因为癌细胞被定义为“代谢异常系统”。碳水化合物在这种异常癌细胞中通过其代谢和分解代谢酶进行代谢重编程。正常细胞从氧化磷酸化获得能量，而癌细胞从氧化糖酵解获得能量，称为“瓦尔堡效应”。能量代谢的差异在癌细胞的生长、侵袭、免疫逃逸和抗肿瘤药物耐药性中很容易被发现。糖酵解途径在多个酶促步骤中进行，并通过酶的管弦乐反应从一个葡萄糖（Glc）分子产生两个丙酮酸分子。不受控制的糖酵解或异常激活的糖酵解在具有增强的糖酵解蛋白和酶活性水平的癌细胞的代谢中容易观察到。在“瓦尔堡效应”中，肿瘤细胞利用由己糖激酶（HK）、酮-HK-A、Glc-6-磷酸异构酶、6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶、磷酸果糖激酶（PFK）、磷酸-Glc异构酶（PGI）、果糖-二磷酸醛缩酶、磷酸甘油酸（PG）激酶（PGK）1、丙糖磷酸异构酶、PG激酶（PGAM）、甘油醛-3-磷酸脱氢酶、烯醇酶、丙酮酸激酶同工酶M2型（PKM 2）、丙酮酸脱氢酶（PDH）、PDH激酶和乳酸脱氢酶。它们与糖酵解通量有关。参与糖酵解的关键酶与肿瘤发生和耐药性直接相关。在代谢酶中，PKM 2、PGK 1、HK、keto-HK-A和核苷二磷酸激酶也具有蛋白激酶活性。由于糖酵解产生的能量不足，癌细胞倾向于糖酵解产生低ATP水平似乎对癌症生长和自我保护无效。因此，瓦尔堡效应仍然是一个有吸引力的现象，以了解代谢糖酵解有利于癌症。如果考虑到瓦尔堡效应的基本特性，包括基因突变和信号转移，则可以提高抗癌治疗靶点。针对有氧糖酵解和缺氧微环境中的代谢酶的特定疗法已经被开发用于杀死肿瘤细胞。本文就肿瘤特异性瓦尔堡效应的研究进展作一综述。
Aerobic glycolysis is an emerging hallmark of many human cancers, as cancer cells are defined as a “metabolically abnormal system”. Carbohydrates are metabolically reprogrammed by its metabolizing and catabolizing enzymes in such abnormal cancer cells. Normal cells acquire their energy from oxidative phosphorylation, while cancer cells acquire their energy from oxidative glycolysis, known as the “Warburg effect”. Energy–metabolic differences are easily found in the growth, invasion, immune escape and anti-tumor drug resistance of cancer cells. The glycolysis pathway is carried out in multiple enzymatic steps and yields two pyruvate molecules from one glucose (Glc) molecule by orchestral reaction of enzymes. Uncontrolled glycolysis or abnormally activated glycolysis is easily observed in the metabolism of cancer cells with enhanced levels of glycolytic proteins and enzymatic activities. In the “Warburg effect”, tumor cells utilize energy supplied from lactic acid-based fermentative glycolysis operated by glycolysis-specific enzymes of hexokinase (HK), keto-HK-A, Glc-6-phosphate isomerase, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, phosphofructokinase (PFK), phosphor-Glc isomerase (PGI), fructose-bisphosphate aldolase, phosphoglycerate (PG) kinase (PGK)1, triose phosphate isomerase, PG mutase (PGAM), glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase isozyme type M2 (PKM2), pyruvate dehydrogenase (PDH), PDH kinase and lactate dehydrogenase. They are related to glycolytic flux. The key enzymes involved in glycolysis are directly linked to oncogenesis and drug resistance. Among the metabolic enzymes, PKM2, PGK1, HK, keto-HK-A and nucleoside diphosphate kinase also have protein kinase activities. Because glycolysis-generated energy is not enough, the cancer cell-favored glycolysis to produce low ATP level seems to be non-efficient for cancer growth and self-protection. Thus, the Warburg effect is still an attractive phenomenon to understand the metabolic glycolysis favored in cancer. If the basic properties of the Warburg effect, including genetic mutations and signaling shifts are considered, anti-cancer therapeutic targets can be raised. Specific therapeutics targeting metabolic enzymes in aerobic glycolysis and hypoxic microenvironments have been developed to kill tumor cells. The present review deals with the tumor-specific Warburg effect with the revisited viewpoint of recent progress.
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4.6
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影响因子：
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影响因子：
3.7
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