title: Mechanisms of RAS/β-catenin interactions.
abstract: Signaling through the WNT/β-catenin and the RAS (rat sarcoma)/MAPK (mitogen-activated protein kinase) pathways plays a key role in the regulation of various physiological cellular processes including proliferation, differentiation, and cell death. Aberrant mutational activation of these signaling pathways is closely linked to the development of cancer in many organs, in humans as well as in laboratory animals. Over the past years, more and more evidence for a close linkage of the two oncogenic signaling cascades has accumulated. Using different experimental approaches, model systems, and experimental conditions, a variety of molecular mechanisms have been identified by which signal transduction through WNT/β-catenin and RAS interact, either in a synergistic or an antagonistic manner. Mechanisms of interaction comprise an upstream crosstalk at the level of pathway-activating ligands and their receptors, interrelations of cytosolic kinases involved in either pathways, as well as interaction in the nucleus related to the joint regulation of target gene transcription. Here, we present a comprehensive review of the current knowledge on the interaction of RAS/MAPK- and WNT/β-catenin-driven signal transduction in mammalian cells.
authors.affiliation: Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Zeller
authors.forename: Katharina
authors.initials: K
authors.lastname: Hammer
authors.forename: Melissa
authors.initials: M
authors.lastname: Kirschnick
authors.forename: Albert
authors.initials: A
authors.lastname: Braeuning
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D020239:Receptor Cross-Talk; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins