title: The Function of V-ATPases in Cancer.
abstract: The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP hydrolysis to proton transport into intracellular compartments and across the plasma membrane. They function in a wide array of normal cellular processes, including membrane traffic, protein processing and degradation, and the coupled transport of small molecules, as well as such physiological processes as urinary acidification and bone resorption. The V-ATPases have also been implicated in a number of disease processes, including viral infection, renal disease, and bone resorption defects. This review is focused on the growing evidence for the important role of V-ATPases in cancer. This includes functions in cellular signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in the highly acidic environment of tumors, aiding the development of drug resistance, as well as crucial roles in tumor cell invasion, migration, and metastasis. Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V-ATPases that function in cancer cells.
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, and Program in Cellular and Molecular Physiology, Program in Biochemistry, and Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Stransky
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, and Program in Cellular and Molecular Physiology, Program in Biochemistry, and Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts.
authors.forename: Kristina
authors.initials: K
authors.lastname: Cotter
authors.affiliation: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, and Program in Cellular and Molecular Physiology, Program in Biochemistry, and Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts.
authors.forename: Michael
authors.initials: M
authors.lastname: Forgac
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases