Fig. 7
From: Gasdermin E regulates the stability and activation of EGFR in human non-small cell lung cancer cells
GSDME knockdown inhibits EGFRY1173 phosphorylation. A, B Western blot analysis of phosphorylated EGFR (Y1173), EGFR and GSDME levels in GSDME-depleted H1792 and H157 cells treated with or without 5 ng/mL EGF/5 min (H1792) and 100 ng/mL EGF/2 min (H157), respectively. β-Actin was used as the loading control. C Working model for regulation of GSDME and EGFR. Full-length GSDME (GSDME-FL) promotes cell proliferation by enhancing and maintaining EGFR signaling. GSDME-FL enhances EGFR signaling by promoting EGFR dimerization. GSDME-FL maintains EGFR signaling by physically interacting with EGFR and covering the EGFRY1045 site, which contributes to its stabilization. When cells are treated with chemotherapeutic agents (such as doxorubicin), caspase-3 cleaves GSDME at Asp270 and releases the GSDME N-terminal fragment. Cleavage allows the GSDME pore-forming domain (GSDME-N) to perforate the plasma membrane and induce pyroptosis. Moreover, GSDME-N binds to EGFR on the membrane and promotes EGFR degradation