title: Filamin acts as a key regulator in epithelial defence against transformed cells.
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.
authors: 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.
authors: Mihoko
authors: M
authors: Kajita
authors: 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.
authors: Kaoru
authors: K
authors: Sugimura
authors: 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.
authors: Atsuko
authors: A
authors: Ohoka
authors: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK.
authors: Jemima
authors: J
authors: Burden
authors: 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.
authors: Hitomi
authors: H
authors: Suganuma
authors: Genomics, Proteomics and Biomedical Functions, Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyoto 610-0394, Japan.
authors: Masaya
authors: M
authors: Ikegawa
authors: Shimadzu Corporation, Life Science Research Center, Tokyo 101-8448, Japan.
authors: Takashi
authors: T
authors: Shimada
authors: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Hokkaido 060-8586, Japan.
authors: Tetsuya
authors: T
authors: Kitamura
authors: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Hokkaido 060-8586, Japan.
authors: Masanobu
authors: M
authors: Shindoh
authors: 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.
authors: Susumu
authors: S
authors: Ishikawa
authors: 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.
authors: Sayaka
authors: S
authors: Yamamoto
authors: 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.
authors: Sayaka
authors: S
authors: Saitoh
authors: 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.
authors: Yuta
authors: Y
authors: Yako
authors: Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido 060-0814, Japan.
authors: Ryosuke
authors: R
authors: Takahashi
authors: Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido 060-0814, Japan.
authors: Takaharu
authors: T
authors: Okajima
authors: Department of Immunology and Cell Biology, Graduate School of Medicine Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors: Junichi
authors: J
authors: Kikuta
authors: Department of Immunology and Cell Biology, Graduate School of Medicine Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors: Yumiko
authors: Y
authors: Maijima
authors: 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.
authors: Masaru
authors: M
authors: Ishii
authors: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors: Masazumi
authors: M
authors: Tada
authors: 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.
authors: Yasuyuki
authors: Y
authors: Fujita
mesh_terms: D000818:Animals; D016923:Cell Death; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D004625:Embryo, Nonmammalian; D064448:Filamins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D061985:Madin Darby Canine Kidney Cells; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014170:Transformation, Genetic; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D064448:Filamins; D034741:RNA, Small Interfering; D014746:Vimentin; D016392:Proto-Oncogene Proteins pp60(c-src); D054460:rho-Associated Kinases; D016283:Proto-Oncogene Proteins p21(ras)