Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells

Mihoko Kajita, Catherine Hogan, Andrew R Harris, Sophie Dupre-Crochet, Nobue Itasaki, Koichi Kawakami, Guillaume Charras, Masazumi Tada, Yasuyuki Fujita

Research output: Contribution to journalArticle (Academic Journal)peer-review

114 Citations (Scopus)
309 Downloads (Pure)

Abstract

At the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial sheet. However, it remains unknown what happens at the boundary between normal and transformed cells. Using Madin-Darby canine kidney (MDCK) cells transformed with temperature-sensitive v-Src, we have examined the interface between normal and Src-transformed epithelial cells. We show that Src-transformed cells are apically extruded when surrounded by normal cells, but not when Src cells alone are cultured, suggesting that apical extrusion occurs in a cell-context-dependent manner. We also observe apical extrusion of Src-transformed cells in the enveloping layer of zebrafish gastrula embryos. When Src-transformed MDCK cells are surrounded by normal MDCK cells, myosin-II and focal adhesion kinase (FAK) are activated in Src cells, which further activate downstream mitogen-activated protein kinase (MAPK). Importantly, activation of these signalling pathways depends on the presence of surrounding normal cells and plays a crucial role in apical extrusion of Src cells. Collectively, these results indicate that interaction with surrounding normal epithelial cells influences the signalling pathways and behaviour of Src-transformed cells.

Original languageEnglish
Pages (from-to)171-180
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number2
Early online date21 Dec 2009
DOIs
Publication statusPublished - 15 Jan 2010

Keywords

  • Animals
  • Cadherins
  • Cell Adhesion
  • Cell Communication
  • Cell Polarity
  • Cell Transformation, Neoplastic
  • Dogs
  • Epithelial Cells
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Mitogen-Activated Protein Kinases
  • Models, Biological
  • Myosin Type II
  • Oncogene Protein pp60(v-src)
  • Protein Transport
  • Signal Transduction
  • Zebrafish
  • beta Catenin

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