title: Death pathways triggered by activated Ras in cancer cells.
abstract: Ras GTPases are best known for their ability to serve as molecular switches regulating cell growth, differentiation and survival. Gene mutations that result in expression of constitutively active forms of Ras have been linked to oncogenesis in animal models and humans. However, over the past two decades, evidence has gradually accumulated to support a paradoxical role for Ras proteins in the initiation of cell death pathways. In this review we survey the literature pointing to the ability of activated Ras to promote cell death under conditions where cancer cells encounter apoptotic stimuli or Ras is ectopically expressed. In some of these cases Ras acts through known effectors and well defined apoptotic death pathways. However, in other cases it appears that Ras operates by triggering novel non-apoptotic death mechanisms that are just beginning to be characterized. Understanding these mechanisms and the factors that go into changing the nature of Ras signaling from pro-survival to pro-death could set the stage for development of novel therapeutic approaches aimed at manipulating pro-death Ras signaling pathways in cancer.
authors.affiliation: Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.
authors.forename: Jean H
authors.initials: JH
authors.lastname: Overmeyer
authors.forename: William A
authors.initials: WA
authors.lastname: Maltese
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology; D016923:Cell Death / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology; D018631:ras Proteins / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D020662:Guanine Nucleotide Exchange Factors; D019253:Proto-Oncogene Proteins c-bcl-2; C411762:RASSF1 protein, human; C454042:RASSF5 protein, human; D025521:Tumor Suppressor Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020559:Monomeric GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D018631:ras Proteins