Metformin inhibits glioma cells stemness and epithelial-mesenchymal transition via regulating YAP activity.

This work aims to study the roles and mechanisms of metformin in glioma cells stemness and epithelial-mesenchymal transition. Here, we found that metformin suppressed glioma cells spheroid formation and size, inhibited the expression of glioma stemness-related marker, CD133. Additionally, Metformin attenuated TGF-β-induced epithelial-mesenchymal transition in glioma cells. Mechanistically, metformin inhibited the nuclear abundance of YAP, a key effector of Hippo pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP transcriptional modulating activity. Importantly, overexpression of a mutant form of YAP (YAP-5SA) attenuated the inhibition of metformin on glioma cells stemness and epithelial-mesenchymal transition. Thus, metformin inhibits glioma cells stemness and epithelial-mesenchymal transition via regulating YAP activity.