Norman, M and Wisniewska, KA and Lawrenson, K and Garcia-Miranda, P and Tada, M and Kajita, M and Mano, H and Ishikawa, S and Ikegawa, M and Shimada, T and Fujita, Y (2012) Loss of Scribble causes cell competition in mammalian cells. J Cell Sci , 125 (Pt 1) 59 - 66. 10.1242/jcs.085803.
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.
|Title:||Loss of Scribble causes cell competition in mammalian cells.|
|Open access status:||An open access publication|
|Additional information:||PMCID: PMC3269023|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
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