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

Nat Commun. 2014 Jul 31;5:4428. doi: 10.1038/ncomms5428.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Dogs
  • Embryo, Nonmammalian
  • Filamins / antagonists & inhibitors
  • Filamins / genetics*
  • Filamins / metabolism
  • Gene Expression Regulation*
  • Madin Darby Canine Kidney Cells
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / genetics
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transformation, Genetic
  • Vimentin / antagonists & inhibitors
  • Vimentin / genetics*
  • Vimentin / metabolism
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Filamins
  • RNA, Small Interfering
  • Vimentin
  • Proto-Oncogene Proteins pp60(c-src)
  • rho-Associated Kinases
  • Proto-Oncogene Proteins p21(ras)