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Nat Commun. 2014 Jul 31;5:4428. doi: 10.1038/ncomms5428.

Filamin acts as a key regulator in epithelial defence against transformed cells.

Author information

1
Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
2
1] Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan [2] JST, PRESTO, 5 Sanban-cho, Chiyoda-ku, Tokyo 102-0075, Japan.
3
MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK.
4
Genomics, Proteomics and Biomedical Functions, Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyoto 610-0394, Japan.
5
Shimadzu Corporation, Life Science Research Center, Tokyo 101-8448, Japan.
6
Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Hokkaido 060-8586, Japan.
7
Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido 060-0814, Japan.
8
Department of Immunology and Cell Biology, Graduate School of Medicine Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
9
1] Department of Immunology and Cell Biology, Graduate School of Medicine Frontier Biosciences, Osaka University, Osaka 565-0871, Japan [2] WPI-Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan [3] JST, CREST, 5 Sanban-cho, Chiyoda-ku, Tokyo 102-0075, Japan.
10
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
11
1] Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan [2] MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK [3] Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.

Abstract

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.

PMID:
25079702
DOI:
10.1038/ncomms5428
[Indexed for MEDLINE]
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