RRC ID 49586
著者 Schimizzi GV, Maher MT, Loza AJ, Longmore GD.
タイトル Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.
ジャーナル PLoS One
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.
巻・号 11(7)
ページ e0159881
公開日 2016-7-25
DOI 10.1371/journal.pone.0159881
PII PONE-D-16-11432
PMID 27454609
PMC PMC4959776
MeSH Adaptor Proteins, Signal Transducing / metabolism* Animals Cell Proliferation Drosophila Proteins / metabolism* Epithelial Cells / metabolism Epithelium / metabolism* MAP Kinase Signaling System Membrane Proteins Mitogen-Activated Protein Kinases / metabolism Multiprotein Complexes / metabolism Myosins / metabolism Protein Binding Protein Kinase C / metabolism* Tumor Suppressor Proteins / metabolism* cdc42 GTP-Binding Protein / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism rho GTP-Binding Proteins / metabolism rho-Associated Kinases / metabolism
IF 2.74
引用数 3
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