Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 6551, Lubbock, TX 79430-6551, USA.
Curr Protein Pept Sci. 2012 Mar;13(2):152-63. doi: 10.2174/138920312800493197.
Up-regulated aerobic glycolysis is a hallmark of malignant cancers. Little is understood about the reasons why malignant tumors up-regulate glycolysis and acidify their microenvironment. Signaling pathways involved in glucose changes are numerous. However, the identity of the internal glucose signal remains obscure. In this review we address the question of the significance of vacuolar proton ATPase (V-ATPase) and its relationship to up-regulated glycolysis in tumors. We know that glycolysis is extremely sensitive to changes in pH. Importantly, the V-ATPase activity is sensitive to glucose availability. Therefore, we propose that pH acts as the glucose signal via the V-ATPase that responds to changes in intracellular pH and acts as a sensor. We hypothesize that the increase in glycolysis leads to intracellular acidification and activates the V-ATPase to maintain a more alkaline intracellular pH in tumors by up-regulating glycolysis. This review attempts to provide a comprehensive description of the current knowledge about the role of V-ATPase in cancer, highlighting its role as a key player in the pH signaling pathway.
有氧糖酵解上调是恶性癌症的一个标志。目前对于恶性肿瘤上调糖酵解并酸化其微环境的原因还知之甚少。涉及葡萄糖变化的信号通路很多。然而，内部葡萄糖信号的身份仍然不清楚。在这篇综述中，我们探讨了液泡质子 ATP 酶（V-ATPase）及其与肿瘤中糖酵解上调的关系的重要性。我们知道糖酵解对 pH 值的变化非常敏感。重要的是，V-ATPase 活性对葡萄糖的可用性敏感。因此，我们提出 pH 值通过 V-ATPase 作为葡萄糖信号发挥作用，V-ATPase 响应细胞内 pH 值的变化并作为传感器发挥作用。我们假设糖酵解的增加会导致细胞内酸化，并通过上调糖酵解来激活 V-ATPase，以维持肿瘤中更碱性的细胞内 pH 值。这篇综述试图提供对 V-ATPase 在癌症中的作用的全面描述，强调其作为 pH 信号通路关键参与者的作用。
