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Integrin switching plays a critical role in the progression to metastatic disease, but the mechanism by which it contributes remains poorly understood. In the 11 February 2014 issue of Science Signaling, Truong et al. identified a transforming growth factor-β-mediated, prometastatic switch that is activated by β1 integrin inhibition in triple-negative breast cancers (TNBCs). Their work provides insight into the complex signaling changes that arise from integrin switching. Further characterization of β-integrin switching will require elucidation of the distribution of specific α-β integrin heterodimers and the role of ligand binding. Identifying the nature of the molecular interactions and the influence of a specific oncogenic context, including the status of driver mutations such as those in Myc and p53, will define the next phase in integrin cancer biology.