Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1

SummaryThe epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.

► Prrx1 is an epithelial-mesenchymal transition inducer in embryos and cancer cells
► Prrx1 cooperates with Twist1 for invasion in embryonic and cancer cells
► Prrx1 loss reverts EMT & induces stemness, both required for metastatic colonization
► High Prrx1 expression associates with good prognosis