Memo mediates ErbB2-driven cell motility

• Published in: Nature cell biology Vol. 6; no. 6; pp. 515 - 522
• Main Authors: Hynes, Nancy E, Marone, Romina, Hess, Daniel, Dankort, David, Muller, William J, Badache, Ali
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-06-2004
• Subjects: Actin Cytoskeleton - metabolism; Carrier Proteins - metabolism; Cell Movement - physiology; Cell receptors; Cells; Cellular signal transduction; Fibers; Genetic aspects; Humans; Membrane Proteins - isolation & purification; Membrane Proteins - metabolism; Mitogen-Activated Protein Kinases - metabolism; Motility; Neoplasm Invasiveness - genetics; Neoplasm Metastasis - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Physiological aspects; Pseudopodia - metabolism; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Signal Transduction - genetics; src-Family Kinases - metabolism; Tumor Cells, Cultured; Canada; United States; Switzerland
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb1134

Clinical studies have revealed that cancer patients whose tumours have increased ErbB2 expression tend to have more aggressive, metastatic disease, which is associated with parameters predicting a poor outcome. The molecular basis underlying ErbB2-dependent cell motility and metastases formation, however, still remains poorly understood. In this study, we show that activation of a set of signalling molecules, including MAPK, phosphatidylinositol-3-OH kinase (PI(3)K) and Src, is required for Neu/ErbB2-dependent lamellipodia formation and for motility of breast carcinoma cells. Stimulation of these molecules, however, failed to induce efficient cell migration in the absence of Neu/ErbB2 phosphorylation at Tyr 1201 or Tyr 1227. We describe a novel molecule, Memo (mediator of ErbB2-driven cell motility), that interacts with a phospho-Tyr 1227-containing peptide, most probably through the Shc adaptor protein. After Neu/ErbB2 activation, Memo-defective cells form actin fibres and grow lamellipodia, but fail to extend microtubules towards the cell cortex. Our data suggest that Memo controls cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton.