title: Vacuolar H(+)-ATPase signaling pathway in cancer.
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.
authors: Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 6551, Lubbock, TX 79430-6551, USA. Souad.Sennoune@ttuhsc.edu
authors: Souad R
authors: SR
authors: Sennoune
authors: Raul
authors: R
authors: Martinez-Zaguilan
mesh_terms: D000818:Animals; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008958:Models, Molecular; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D021122:Protein Subunits / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D025262:Vacuolar Proton-Translocating ATPases / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051793:Hypoxia-Inducible Factor 1; D021122:Protein Subunits; D051153:Wnt Proteins; D051176:beta Catenin; D025262:Vacuolar Proton-Translocating ATPases