EMT and MET: necessary or permissive for metastasis?

Abstract

ABSTRACTEpithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition (MET) have been often suggested to play crucial roles in metastatic dissemination of carcinomas. Recent studies have revealed that neither of these processes is binary. Instead, carcinoma cells often exhibit a spectrum of epithelial/mesenchymal phenotype(s). While epithelial-mesenchymal plasticity has been observed pre-clinically and clinically, whether any of these phenotypic transitions are indispensable for metastatic outgrowth remains an unanswered question. Here, we focus on epithelial-mesenchymal plasticity in metastatic dissemination and propose alternative mechanisms for successful dissemination and metastases beyond the traditional EMT-MET view. We highlight multiple hypotheses that can help reconcile conflicting observations, and outline the next set of key questions that can offer valuable insights into mechanisms of metastasis in multiple tumor models.