scholarly journals Growth Inhibition by Insulin-like Growth Factor-binding Protein-3 in T47D Breast Cancer Cells Requires Transforming Growth Factor-β (TGF-β) and the Type II TGF-β Receptor

2000 ◽  
Vol 275 (50) ◽  
pp. 39146-39151 ◽  
Author(s):  
Susan Fanayan ◽  
Sue M. Firth ◽  
Alison J. Butt ◽  
Robert C. Baxter
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type Ii ◽  
Factor Binding ◽  
Β Receptor

scholarly journals Signaling through ShcA Is Required for Transforming Growth Factor β- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion

2008 ◽  
Vol 28 (10) ◽  
pp. 3162-3176 ◽  
Author(s):  
Jason J. Northey ◽  
Juliann Chmielecki ◽  
Elaine Ngan ◽  
Caterina Russo ◽  
Matthew G. Annis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Motility ◽  
Cancer Cells ◽  
Mammary Tumor ◽  
Breast Cancer Cells ◽  
Transforming Growth Factor ◽  
Adaptor Protein ◽  
Transforming Growth Factor Β ◽  
Migration And Invasion

ABSTRACT Cooperation between the Neu/ErbB-2 and transforming growth factor β (TGF-β) signaling pathways enhances the invasive and metastatic capabilities of breast cancer cells; however, the underlying mechanisms mediating this synergy have yet to be fully explained. We demonstrate that TGF-β induces the migration and invasion of mammary tumor explants expressing an activated Neu/ErbB-2 receptor, which requires signaling from autophosphorylation sites located in the C terminus. A systematic analysis of mammary tumor explants expressing Neu/ErbB-2 add-back receptors that couple to distinct signaling molecules has mapped the synergistic effect of TGF-β-induced motility and invasion to signals emanating from tyrosine residues 1226/1227 and 1253 of Neu/ErbB-2. Given that the ShcA adaptor protein is known to interact with Neu/ErbB-2 through these residues, we investigated the importance of this signaling molecule in TGF-β-induced cell motility and invasion. The reduction of ShcA expression rendered cells expressing activated Neu/ErbB-2, or add-back receptors signaling specifically through tyrosines 1226/1227 or 1253, unresponsive to TGF-β-induced motility and invasion. In addition, a dominant-negative form of ShcA, lacking its three known tyrosine phosphorylation sites, completely abrogates the TGF-β-induced migration and invasion of breast cancer cells expressing activated Neu/ErbB-2. Our results implicate signaling through the ShcA adaptor as a key component in the synergistic interaction between these pathways.

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