LSD1 engaged ERα activation orchestrates the formation of migrasomes to promote gastric cancer metastasis

Abstract

The lysine specific demethylase 1 (LSD1) plays a vital role in promoting various malignancies, while the role of LSD1 in gastric cancer (GC) remains poorly understood. Herein, we show the critical role of LSD1 in GC migration. The overexpression of LSD1 in GC tissues, particularly in those with metastasis, indicates its potential in driving GC migration. Further mechanism study revealed that LSD1, a coregulator of ERα, is involved in the transcriptional regulation of ERα target genes, highlighting the significance of LSD1 and ERα in promoting GC cell migration. We characterized that LSD1 and ERα activation facilitated GC cell migration by promoting the generation of migrasomes mediated by the upregulated fibronectin (FN1). Upon LSD1 abrogation, a substantial decrease in the expression levels of TSPAN4 and NDST1, recognized markers of migrasomes, was observed. Our findings reveal a novel mechanism involving the interaction between LSD1, ERα, FN1 and migrasomes in facilitating GC migration.

Keywords: Gastric cancer; LSD1; Migrasome.