MicroRNAs: Cobblestones on the road to cancer metastasis

Cancer metastasis is the product of a multistep process during which tumor cells, responding to different intrinsic and extrinsic stimuli, detach from the primary tumor mass, invade the contiguous stroma, migrate over a long distance, and colonize distant organs. Despite the well-established role of protein-coding genes behind such events, emerging evidence suggests how genetic and epigenetic alterations in microRNAs equally contribute to cancer metastasis. In this review, we retrace step-to-step all the most salient phases of the tumor dissemination process, by focusing on the role that specific microRNAs play from the time a cancer cell leaves the primary tumor until it acquires the ability to form secondary tumors at distant sites. We also provide a discussion of relevant conceptual and technological issues that need to be addressed before a microRNA-based therapy might be exploited in the clinical setting for the prevention and cure of the metastatic disease.