Grb2 signaling in cell motility and cancer

Background: Metastasis is the primary cause of death in most human cancers, and understanding the molecular mechanisms underpinning this multistep process is fundamental to identifying novel molecular targets and developing more effective therapies. Objective/methods: Here we review the role of growth factor receptor-bound protein 2 (Grb2) in cancer and specifically in metastasis-related processes, and summarize the development of anticancer therapeutics selectively targeting this adapter protein. Results/conclusion: Grb2 is a key molecule in intracellular signal transduction, linking activated cell surface receptors to downstream targets by binding to specific phosphotyrosine-containing and proline-rich sequence motifs. Grb2 signaling is critical for cell cycle progression and actin-based cell motility, and, consequently, more complex processes such as epithelial morphogenesis, angiogenesis and vasculogenesis. These functions make Grb2 a therapeutic target for strategies designed to prevent the spread of solid tumors through local invasion and metastasis.