Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication.
Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication.
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DOI：
10.4331/wjbc.v6.i3.148
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发表时间：
2015-08-26
期刊：
影响因子：
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通讯作者：
Yoon, Jung-Hwan
中科院分区：
文献类型：
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作者：
Lee, Minjong;Yoon, Jung-Hwan
有氧糖酵解，即瓦尔堡效应，可能导致肝细胞癌的侵袭性表型。然而，越来越多的证据凸显了瓦尔堡效应的局限性，例如癌细胞中线粒体呼吸较高和糖酵解率较低。为了解释这种与瓦尔堡效应有关的矛盾现象，提出了糖酵解细胞和氧化细胞之间的代谢相互作用，即“反向瓦尔堡效应”。有氧糖酵解也可能发生在肿瘤周围的基质室中。因此，基质细胞为癌细胞提供乳酸，这种相互作用可以防止肿瘤微环境中形成酸性条件。这一概念提供了肿瘤的巨大异质性，这使得该疾病难以使用单一药物治愈。了解乳酸梭的代谢灵活性为开发针对缺氧肿瘤微环境并克服糖酵解抑制剂的局限性的治疗方法提供了新的视角。
Aerobic glycolysis, i.e., the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e., the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.