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

Author

Listed:
  • 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
    JST, PRESTO, 5 Sanban-cho, Chiyoda-ku)

  • 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
    WPI-Immunology Frontier Research Center, Osaka University
    JST, CREST, 5 Sanban-cho, Chiyoda-ku)

  • Masazumi Tada

    (University College London)

  • Yasuyuki Fujita

    (Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering
    MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London
    University College London)

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.

Suggested Citation

  • Mihoko Kajita & Kaoru Sugimura & Atsuko Ohoka & Jemima Burden & Hitomi Suganuma & Masaya Ikegawa & Takashi Shimada & Tetsuya Kitamura & Masanobu Shindoh & Susumu Ishikawa & Sayaka Yamamoto & Sayaka Sa, 2014. "Filamin acts as a key regulator in epithelial defence against transformed cells," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5428
    DOI: 10.1038/ncomms5428
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    Cited by:

    1. Kazuki Nakai & Hancheng Lin & Shotaro Yamano & Shinya Tanaka & Sho Kitamoto & Hitoshi Saitoh & Kenta Sakuma & Junpei Kurauchi & Eilma Akter & Masamitsu Konno & Kojiro Ishibashi & Ryo Kamata & Akihiro , 2023. "Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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