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

细丝蛋白是上皮细胞防御转化细胞的关键调节剂

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作者: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 Ta

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.

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