Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/?catenin complex in cells transformed with a temperature-sensitive v-SRC gene

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Item Type:	Article
Title:	Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/?catenin complex in cells transformed with a temperature-sensitive v-SRC gene
Creators Name:	Behrens, J., Vakaet, L., Friis, R., Winterhager, E., van Roy, F., Mareel, M.M. and Birchmeier, W.
Abstract:	Loss of histotypic organization of epithelial cells is a common feature in normal development as well as in the invasion of carcinomas. Here we show that the v-src oncogene is a potent effector of epithelial differentiation and invasiveness. MDCK epithelial cells transformed with a temperature-sensitive mutant of v-src exhibit a strictly epithelial phenotype at the nonpermissive temperature for pp60v-src activity (40.5 degrees C) but rapidly loose cell-to-cell contacts and acquire a fibroblast-like morphology after culture at the permissive temperature (35 degrees C). Furthermore, the invasiveness of the cells into collagen gels or into chick heart fragments was increased at the permissive temperature. The profound effects of v-src on intercellular adhesion were not linked to changes in the levels of expression of the epithelial cell adhesion molecule E-cadherin. Rather, we observed an increase in tyrosine phosphorylation of E-cadherin and, in particular, of the associated protein beta-catenin. These results suggest a mechanism by which v-src counteracts junctional assembly and thereby promotes invasiveness and dedifferentiation of epithelial cells through phosphorylation of the E-cadherin/catenin complex.
Keywords:	Cadherins, Cell Differentiation, Transformed Cell Line, Neoplastic Cell Transformation, Cytoskeletal Proteins, Epithelial Cells, Epithelium, src Genes, Kidney, Myocardium, Neoplasm Invasiveness, Organ Culture Techniques, Phosphorylation, Temperature, Trans-Activators, Transfection, beta Catenin, Animals, Chick Embryo, Dogs
Source:	Journal of Cell Biology
ISSN:	0021-9525
Publisher:	Rockefeller University Press
Volume:	120
Number:	3
Page Range:	757-766
Date:	February 1993
Official Publication:	https://doi.org/10.1083/jcb.120.3.757
PubMed:	View item in PubMed

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