The epidermal growth factor receptor modulates the interaction of E- cadherin with the actin cytoskeleton

Rachel Hazan, Larry Norton

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E- cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB- 468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-468 cells, and this treatment stimulated the interaction of actin, α-actinin, and vinculin with E-cadherin complexes, despite the absence of α-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several α-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (β- catenin, plakoglobin/γ-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, α-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of β-catenin, plakoglobin/γ-catenin and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum- treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.

Original languageEnglish (US)
Pages (from-to)9078-9084
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number15
DOIs
StatePublished - Apr 10 1998
Externally publishedYes

Fingerprint

Cadherins
Catenins
Actin Cytoskeleton
Epidermal Growth Factor Receptor
Actins
Vinculin
gamma Catenin
Epidermal Growth Factor
Actinin
Agglomeration
Cell adhesion
Cell Adhesion
Cell Line
Tumors
Serum
Cells
Cell Aggregation
Phosphorylation
Molecules
Blocking Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

The epidermal growth factor receptor modulates the interaction of E- cadherin with the actin cytoskeleton. / Hazan, Rachel; Norton, Larry.

In: Journal of Biological Chemistry, Vol. 273, No. 15, 10.04.1998, p. 9078-9084.

Research output: Contribution to journalArticle

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abstract = "Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E- cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB- 468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-468 cells, and this treatment stimulated the interaction of actin, α-actinin, and vinculin with E-cadherin complexes, despite the absence of α-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several α-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (β- catenin, plakoglobin/γ-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, α-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of β-catenin, plakoglobin/γ-catenin and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum- treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.",
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