title: Loss of Scribble causes cell competition in mammalian cells.
abstract: In Drosophila, normal and transformed cells compete with each other for survival in a process called cell competition. However, it is not known whether comparable phenomena also occur in mammals. Scribble is a tumor suppressor protein in Drosophila and mammals. In this study we examine the interface between normal and Scribble-knockdown epithelial cells using Madin-Darby Canine Kidney (MDCK) cells expressing Scribble short hairpin RNA (shRNA) in a tetracycline-inducible manner. We observe that Scribble-knockdown cells undergo apoptosis and are apically extruded from the epithelium when surrounded by normal cells. Apoptosis does not occur when Scribble-knockdown cells are cultured alone, suggesting that the presence of surrounding normal cells induces the cell death. We also show that death of Scribble-knockdown cells occurs independently of apical extrusion. Finally, we demonstrate that apoptosis of Scribble-knockdown cells depends on activation of p38 mitogen-activated protein kinase (MAPK). This is the first demonstration that an oncogenic transformation within an epithelium induces cell competition in a mammalian cell culture system.
authors.affiliation: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Norman
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Wisniewska
authors.forename: Kate
authors.initials: K
authors.lastname: Lawrenson
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Miranda
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kajita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mano
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Ikegawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D016764:Cell Polarity; D048430:Cell Shape; D004285:Dogs; D029721:Drosophila Proteins; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C404683:Scrib protein, Drosophila; D048051:p38 Mitogen-Activated Protein Kinases