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J Cell Sci. 2010 Jan 15;123(Pt 2):171-80. doi: 10.1242/jcs.057976. Epub 2009 Dec 21.

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

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1
MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, WC1E 6BT, UK.

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.

PMID:
20026643
PMCID:
PMC2954245
DOI:
10.1242/jcs.057976
[Indexed for MEDLINE]
Free PMC Article
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