title: Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.
abstract: The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin.
authors.affiliation: ICCE Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Schimizzi
authors.affiliation: ICCE Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Meghan T
authors.initials: MT
authors.lastname: Maher
authors.affiliation: ICCE Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Computational and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Loza
authors.affiliation: ICCE Institute, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.|Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; C070350:dlg1 protein, Drosophila; D054460:rho-Associated Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D009218:Myosins; C511153:Rho1 protein, Drosophila; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins