期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 1, 页码 59-66出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.085803
关键词
MDCK cells; Scribble; Cell competition; p38 MAPK
类别
资金
- Medical Research Council
- Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Takeda Science Foundation
- Naito Foundation
- Sagawa Foundation for promotion of Cancer Research
- Yasuda Medical Foundation
- Ono Cancer Research Fund
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Ichiro Kanehara Foundation
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.
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