Cancer and Microenvironment Plasticity: Double-Edged Swords in Metastasis

Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate microenvironmental components by reshaping them into accomplices of metastasis. Recent studies have identified a plethora of new molecular and cellular modulators of metastasis that have dynamic or even opposite roles, dominating the phenotypic plasticity of both tumoral and microenvironmental components. In this review we discuss their bipotential functions and the possible underpinning mechanisms, as well as their implications for targeted cancer therapy.