Fig. 8
A schematic diagram illustrates the potential mechanism by which ETAR drives YAP/ZEB1 signaling network to promote metastatic traits in HG-SOC cells. ETAR activation by ET-1 increases ILK expression which, in turn, promotes the YAP/ZEB1 nuclear accumulation. In the nucleus, YAP and ZEB1 are engaged in an active transcriptional complex with AP-1 that favors the ZEB1 and ET-1 production, thereby creating a feed-forward loop that sustains a persistent ET-1/ETAR signaling activity. YAP/ZEB1 interplay is involved in ET-1R/ILK-induced EMT, cellular plasticity, and cell invasion. ETAR blockade with macitentan, curbing the ZEB1/YAP transcriptional activity, prevents HG-SOC metastatic progression. Part of the figure is drawn using pictures from Servier Medical Art (https://smart.servier.com), licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0)