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

@article{citeulike:2741545, abstract = {Cooperation between the Neu/ErbB-2 and transforming growth factor (TGF-) 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- 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--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--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--induced motility and invasion. In addition, a dominant-negative form of ShcA, lacking its three known tyrosine phosphorylation sites, completely abrogates the TGF--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. 10.1128/MCB.01734-07}, author = {Northey, Jason J. and Chmielecki, Juliann and Ngan, Elaine and Russo, Caterina and Annis, Matthew G. and Muller, William J. and Siegel, Peter M. }, citeulike-article-id = {2741545}, doi = {10.1128/MCB.01734-07}, journal = {Mol. Cell. Biol.}, month = {May}, number = {10}, pages = {3162--3176}, posted-at = {2008-05-01 03:23:07}, priority = {2}, title = {Signaling through ShcA Is Required for Transforming Growth Factor {beta}- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion}, url = {http://dx.doi.org/10.1128/MCB.01734-07}, volume = {28}, year = {2008} }

TY - JOUR ID - citeulike:2741545 L3 - citeulike-article-id:2741545 TI - Signaling through ShcA Is Required for Transforming Growth Factor {beta}- and Neu/ErbB-2-Induced Breast Cancer Cell Motility and Invasion JF - Mol. Cell. Biol. VL - 28 IS - 10 SP - 3162 EP - 3176 N2 - Cooperation between the Neu/ErbB-2 and transforming growth factor (TGF-) 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- 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--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--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--induced motility and invasion. In addition, a dominant-negative form of ShcA, lacking its three known tyrosine phosphorylation sites, completely abrogates the TGF--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. 10.1128/MCB.01734-07 AU - Northey, Jason AU - Chmielecki, Juliann AU - Ngan, Elaine AU - Russo, Caterina AU - Annis, Matthew AU - Muller, William AU - Siegel, Peter PY - 2008/05/15/ UR - http://dx.doi.org/10.1128/MCB.01734-07 ER -