Phenotypic plasticity involves a process in which cells transiently acquire 
phenotypic traits of another lineage. Two commonly studied types of phenotypic 
plasticity are epithelial-mesenchymal transition (EMT) and 
mesenchymal-epithelial transition (MET). In carcinomas, EMT drives invasion and 
metastatic dissemination, while MET is proposed to play a role in metastatic 
colonization. Phenotypic plasticity in sarcomas is not well studied; however, 
there is evidence that a subset of sarcomas undergo an MET-like phenomenon. 
While the exact mechanisms by which these transitions occur remain largely 
unknown, it is likely that some of the same master regulators that drive EMT and 
MET in carcinomas also act in sarcomas. In this study, we combined mathematical 
models with bench experiments to identify a core regulatory circuit that 
controls MET in sarcomas. This circuit comprises the microRNA 200 (miR-200) 
family, ZEB1, and GRHL2. Interestingly, combined expression of miR-200s and 
GRHL2 further upregulates epithelial genes to induce MET. This effect is 
phenocopied by downregulation of either ZEB1 or the ZEB1 cofactor, BRG1. In 
addition, an MET gene expression signature is prognostic for improved overall 
survival in sarcoma patients. Together, our results suggest that a miR-200, 
ZEB1, GRHL2 gene regulatory network may drive sarcoma cells to a more 
epithelial-like state and that this likely has prognostic relevance.