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

Mihoko Kajita, Kaoru Sugimura, Atsuko Ohoka, Jemima Burden, Hitomi Suganuma, Masaya Ikegawa, Takashi Shimada, Tetsuya Kitamura, Masanobu Shindoh, Susumu Ishikawa, Sayaka Yamamoto, Sayaka Saitoh, Yuta Yako, Ryosuke Takahashi, Takaharu Okajima, Junichi Kikuta, Yumiko Maijima, Masaru Ishii, Masazumi Tada and Yasuyuki Fujita ()
Additional contact information
Mihoko Kajita: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Kaoru Sugimura: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University
Atsuko Ohoka: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Jemima Burden: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London
Hitomi Suganuma: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Masaya Ikegawa: Genomics, Proteomics and Biomedical Functions, Faculty of Life and Medical Sciences, Doshisha University
Takashi Shimada: Shimadzu Corporation, Life Science Research Center
Tetsuya Kitamura: Hokkaido University Graduate School of Dental Medicine
Masanobu Shindoh: Hokkaido University Graduate School of Dental Medicine
Susumu Ishikawa: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Sayaka Yamamoto: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Sayaka Saitoh: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Yuta Yako: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
Ryosuke Takahashi: Graduate School of Information Science and Technology, Hokkaido University
Takaharu Okajima: Graduate School of Information Science and Technology, Hokkaido University
Junichi Kikuta: Graduate School of Medicine Frontier Biosciences, Osaka University
Yumiko Maijima: Graduate School of Medicine Frontier Biosciences, Osaka University
Masaru Ishii: Graduate School of Medicine Frontier Biosciences, Osaka University
Masazumi Tada: University College London
Yasuyuki Fujita: Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5428

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