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Title
  • en Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells
Creator
    • en Saitoh, Sayaka
    • en Maruyama, Takeshi
    • en Yako, Yuta
    • en Fujioka, Yoichiro
    • en Kasai, Nobuhiro
    • en Sugama, Natsu
    • en Ishikawa, Susumu
    • en Hayashi, Takashi
    • en Yamazaki, Tomohiro
    • en Tada, Masazumi
Accessrights open access
Subject
  • Other en cell competition
  • Other en endocytosis
  • Other en apical extrusion
  • Other en Rab5
  • Other en RasV12
  • NDC 490
Description
  • Abstract en Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by up-regulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals.
Publisher en National Academy of Sciences
Date
    Issued2017-03-21
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/67160
Relation
  • isVersionOf DOI https://doi.org/10.1073/pnas.1602349114
Journal
    • PISSN 0027-8424
      • en Proceedings of the National Academy of Sciences of the United States of America
      • Volume Number114 Issue Number12 Page StartE2327 Page EndE2336
File
Oaidate 2023-07-26