期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5428
关键词
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资金
- Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Ono Cancer Research Fund
- Takeda Science Foundation
- Uehara Memorial Foundation
- Naito Foundation
- Medical Research Council [MC_CF12266] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [14J02420, 26870004, 25286081, 26114008, 26250026, 14J02366] Funding Source: KAKEN
Recent studies have shown that certain types of transformed cells are extruded from an epithelial monolayer. However, it is not known whether and how neighbouring normal cells play an active role in this process. In this study, we demonstrate that filamin A and vimentin accumulate in normal cells specifically at the interface with Src- or RasV12-transformed cells. Knockdown of filamin A or vimentin in normal cells profoundly suppresses apical extrusion of the neighbouring transformed cells. In addition, we show in zebrafish embryos that filamin plays a positive role in the elimination of the transformed cells. Furthermore, the Rho/Rho kinase pathway regulates filamin accumulation and filamin acts upstream of vimentin in the apical extrusion. This is the first report demonstrating that normal epithelial cells recognize and actively eliminate neighbouring transformed cells and that filamin is a key mediator in the interaction between normal and transformed epithelial cells.
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