title: Plasticity of mammary cell boundaries governed by EGF and actin remodeling.
abstract: Defined signals that dictate the architecture of cellular boundaries in confluent cultures are poorly characterized. Here, we report dramatic remodeling, invoked by long-term epidermal growth factor (EGF) withdrawal from mammary-derived MCF10A cells. Such intervention generates an interdigitated, desmosome-rich monolayer, wherein cells project actin-containing protrusions deep into neighboring cells. These changes protect cellular sheets from mechanical disruption and dramatically restrict the freedom of cells to roam within the monolayer. Ectopic expression of activated Rac counteracts interdigitation and induces membrane ruffling, but cells remain confined by their interdigitated neighbors. Interdigitations are rapidly dissolved by acute EGF application in a process that is sensitive to actin depolymerization and myosin II inhibition. These assays for formation and dissolution of interdigitations provide a platform for the dissection of novel signaling pathways that are highly specific to EGF receptor (EGFR) activation.
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Wai Ying Yvonne
authors.initials: WYY
authors.lastname: Tang
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Beckett
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Prior
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Judy M
authors.initials: JM
authors.lastname: Coulson
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK. Electronic address: urbe@liv.ac.uk.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Urbé
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK. Electronic address: clague@liv.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clague
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003896:Desmosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D033081:Shear Strength; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D015820:Cadherins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000077156:Gefitinib