Figure 4.

Mechanisms of EMT reversion. Colonization at distant sites requires the reversion of EMT to promote tumor cell proliferation. The interplay between EMT activators and inhibitors (i.e., MET activators) plays a critical role in metastatic outgrowth. The loss of EMT activators such as Twist1 or Prrx1 appears to be required to promote EMT reversion. However, signals from the microenvironment in distant sites may also shift the balance from EMT activators to EMT inhibitors or MET activators. It is unknown when or how these factors are regulated during tumor progression, which may impact treatment of metastatic disease.