title: Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells.
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.
authors.affiliation: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London, WC1E 6BT, UK.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kajita
authors.forename: Catherine
authors.initials: C
authors.lastname: Hogan
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Harris
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupre-Crochet
authors.forename: Nobue
authors.initials: N
authors.lastname: Itasaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charras
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D016764:Cell Polarity; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D024462:Myosin Type II / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D015027:Zebrafish / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D020928:Mitogen-Activated Protein Kinases; D024462:Myosin Type II