FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells

Tomoko Kamasaki; Yumi Miyazaki; Susumu Ishikawa; Kazuya Hoshiba; Keisuke Kuromiya; Nobuyuki Tanimura; Yusuke Mori; Motosuke Tsutsumi; Tomomi Nemoto; Ryota Uehara; Shiro Suetsugu; Toshiki Itoh; Yasuyuki Fujita

doi:10.1016/j.isci.2021.102994

FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells

iScience. 2021 Aug 18;24(9):102994. doi: 10.1016/j.isci.2021.102994. eCollection 2021 Sep 24.

Authors

Tomoko Kamasaki^{1

2}, Yumi Miyazaki¹, Susumu Ishikawa¹, Kazuya Hoshiba¹, Keisuke Kuromiya^{1

3}, Nobuyuki Tanimura^{1

3}, Yusuke Mori^{1

3}, Motosuke Tsutsumi^{4

5}, Tomomi Nemoto^{4

5}, Ryota Uehara², Shiro Suetsugu⁶, Toshiki Itoh^{7

8}, Yasuyuki Fujita^{1

3}

Affiliations

¹ Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Hokkaido 060-0815, Japan.
² Faculty of Advanced Life Science, Hokkaido University, Sapporo, Hokkaido 001-0021, Japan.
³ Department of Molecular Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
⁴ Research Institute for Electronic Science, Hokkaido University, Sapporo, Hokkaido 001-0020, Japan.
⁵ Exploratory Research Center on Life and Living Systems (ExCELLS) & National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
⁶ Division of Biological Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
⁷ Division of Membrane Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
⁸ Biosignal Research Center, Kobe University, Kobe, Hyogo 657-8501, Japan.

Abstract

At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing "protrusion to protrusion response" between normal and RasV12-transformed cells.

Keywords: Cell biology; Optics; Organizational aspects of cell biology.