Nuclear gasdermin E drives endothelin-1-induced metastatic progression independently of the pyroptosis.

ABSTRACT: Elucidation of the molecular mechanism underlying metastatic dissemination in patients with high-grade serous ovarian carcinoma (HG-SOC) has the potential to affect patient outcome. This study explores the role of gasdermins (GSDMs) in HG-SOC, focusing on novel pyroptosis-independent nuclear functions of GSDME, which are integrated with the endothelin-1 (ET-1)/ET-1 receptor A (ET_AR) signaling to sustain metastatic progression. In this tumor, GSDME upregulation is correlated to epithelial-mesenchymal transition (EMT) and ET_AR expression. ET-1 signaling fuels GSDME expression by inducing its transcription via the core EMT factors, ZEB1 and ZEB2. GSDME, in turn, translocates to the nucleus to engage ZEB1 and transcriptionally regulate genes coupled with EMT and inflammat

SUBMITTER: Roman C 

PROVIDER: S-EPMC12811335 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature