Figure 2.

Breast cancer metastasis dormancy. Maintenance of the latent state of DTCs involves both cell autonomous mechanisms and interactions with other components of bone and tumoral stroma. The variety of signals that are relevant to control this state reveals that tumor dormancy is a complex feature that likely involves not only solitary cell dormancy but also tumor mass dormancy, thereby balancing mitotic and apoptotic events. The innate and adaptive immune systems play a key role in controlling latency. In this setting, inhibition of autocrine Wnt signaling promotes immune evasion and a slow cycling state of the tumor cells. Inhibition of the angiogenic switch also provides an important checkpoint of the dormant state. Numerous cell signaling pathways (including those with MAPKs and PI3K) that respond to exogenous factors (such as hypoxia, TGFβ2, and BMP) mediate a cell response that results in latency maintenance with cell cycle arrest or cell differentiation.