Intravital imaging illuminates transforming growth factor beta signaling switches during metastasis

Transforming growth factor beta (TGFbeta) has seemingly contradictory roles in tumor progression: it can promote metastatic invasion but also act as a tumor suppressor. Recently, two studies have used intravital imaging to unravel the role of TGFbeta at different stages of the metastatic process. TGFbeta promotes single cell motility, which enables invasion into blood vessels. However the activation of TGFbeta signaling is a transient event and is not maintained at distant sites. The downregulation of TGFbeta signaling at secondary sites then permits growth of secondary tumors. In the absence of TGFbeta, cells are restricted to collective movement and lymphatic spread. Here, we discuss these findings and their potential implications.