Abstract
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.
Keywords: V-ATPase, glycolysis, (Pro)Renin Receptor/ATP6ap2, Wnt/β-catenin, hypoxia-inducible factor, metastasis, glycolysis, mitochondria, microenvironment pH, plasmalemmal V-ATPase, embranes
Current Protein & Peptide Science
Title:Vacuolar H+-ATPase Signaling Pathway in Cancer
Volume: 13 Issue: 2
Author(s): Souad R. Sennoune and Raul Martinez-Zaguilan
Affiliation:
Keywords: V-ATPase, glycolysis, (Pro)Renin Receptor/ATP6ap2, Wnt/β-catenin, hypoxia-inducible factor, metastasis, glycolysis, mitochondria, microenvironment pH, plasmalemmal V-ATPase, embranes
Abstract: 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.
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Cite this article as:
R. Sennoune Souad and Martinez-Zaguilan Raul, Vacuolar H+-ATPase Signaling Pathway in Cancer, Current Protein & Peptide Science 2012; 13 (2) . https://dx.doi.org/10.2174/138920312800493197
DOI https://dx.doi.org/10.2174/138920312800493197 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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