title: Epithelial Membrane Protein 2 and β1 integrin signaling regulate APC-mediated processes.
abstract: Adenomatous Polyposis Coli (APC) plays a critical role in cell motility, maintenance of apical-basal polarity, and epithelial morphogenesis. We previously demonstrated that APC loss in Madin Darby Canine Kidney (MDCK) cells increases cyst size and inverts polarity independent of Wnt signaling, and upregulates the tetraspan protein, Epithelial Membrane Protein 2 (EMP2). Herein, we show that APC loss increases β1 integrin expression and migration of MDCK cells. Through 3D in vitro model systems and 2D migration analysis, we have depicted the molecular mechanism(s) by which APC influences polarity and cell motility. EMP2 knockdown in APC shRNA cells revealed that APC regulates apical-basal polarity and cyst size through EMP2. Chemical inhibition of β1 integrin and its signaling components, FAK and Src, indicated that APC controls cyst size and migration, but not polarity, through β1 integrin and its downstream targets. Combined, the current studies have identified two distinct and novel mechanisms required for APC to regulate polarity, cyst size, and cell migration independent of Wnt signaling.
authors.affiliation: Department of Biological Science, Harper Cancer Research Institute, University of Notre Dame, United States.
authors.forename: Alyssa C
authors.initials: AC
authors.lastname: Lesko
authors.affiliation: Department of Biological Science, Harper Cancer Research Institute, University of Notre Dame, United States; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, United States. Electronic address: jrprospe@iupui.edu.
authors.forename: Jenifer R
authors.initials: JR
authors.lastname: Prosperi
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C113388:Emp2 protein, mouse; D019012:Integrin beta1; D008562:Membrane Glycoproteins
keywords: 3D morphology; APC; Apical-basal polarity; EMP2; Migration; β1 integrin