YAP/TAZ inhibition reduces metastatic potential of Ewing sarcoma cells.

ABSTRACT: Ewing sarcoma (EwS) is a highly metastatic bone cancer characterized by the ETS fusion oncoprotein EWS-FLI1. EwS cells are phenotypically highly plastic and switch between functionally distinct cell states dependent on EWS-FLI1 fluctuations. Whereas EWS-FLI1^high cells proliferate, EWS-FLI1^low cells are migratory and invasive. Recently, we reported activation of MRTFB and TEAD, effectors of RhoA and Hippo signalling, upon low EWS-FLI1, orchestrating key steps of the EwS migratory gene expression program. TEAD and its co-activators YAP and TAZ are commonly overexpressed in cancer, providing attractive therapeutic targets. We find TAZ levels to increase in the migratory EWS-FLI1^low state and to associate with adverse prognosis in EwS patients. We tested the ef

SUBMITTER: Bierbaumer L 

PROVIDER: S-EPMC7794350 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature