Regulation of dormancy during tumor dissemination: the role of the ECM

The study of the metastatic cascade has revealed the complexity of the process and the multiple cellular states that disseminated cancer cells must go through. The tumor microenvironment and in particular the extracellular matrix (ECM) plays an important role in regulating the transition from invasion, dormancy to ultimately proliferation during the metastatic cascade. The time delay from primary tumor detection to metastatic growth is regulated by a molecular program that maintains disseminated tumor cells in a non-proliferative, quiescence state known as tumor cell dormancy. Identifying dormant cells and their niches in vivo and how they transition to the proliferative state is an active area of investigation, and novel approaches have been developed to track dormant cells during dissemination. In this review, we highlight the latest research on the invasive nature of disseminated tumor cells and their link to dormancy programs. We also discuss the role of the ECM in sustaining dormant niches at distant sites.