4.7 Article

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

Journal

ISCIENCE
Volume 24, Issue 9, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2021.102994

Keywords

-

Funding

  1. Japan Society for the Promotion of Science (JSPS) [21H05039]
  2. JSPS Bilateral Joint Research Projects (The Royal Society) [JPJSBP1 20215703]
  3. Japan Science and Technology Agency (JST) (Moonshot R D) [JPMJPS2022]
  4. Takeda Science Foundation
  5. SAN-ESU GIKEN CO. LTD
  6. Kazato Research Foundation
  7. Shiseido Female Researcher Science Grant
  8. Hokkaido University Promotion Office of Research Environment for Diversity
  9. Akiyama Life Science Foundation
  10. JSPS [20K21411]
  11. [17K15589]
  12. [19J40132]
  13. [20K07559]
  14. Grants-in-Aid for Scientific Research [21H05039, 20K21411] Funding Source: KAKEN

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Research has found that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface, and FBP17 protein accumulates in RasV12 cells and surrounding normal cells, playing a positive role in the formation of these protrusions and the apical elimination of RasV12 cells. It is also shown that cdc42 acts upstream of these processes, indicating that the cdc42/FBP17 pathway is a crucial trigger of cell competition.
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.

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