Small extracellular vesicles-delivered LSD1 promotes gastric cancer cell stemness

ABSTRACT: Although there are plenty of researches about nucleic acid in small extracellular vesicles (sEVs), properties of proteins identified as sEVs’ cargos and the mechanism of their action in recipient cell are poorly understood. Here, we show that lysine specific demethylase 1 (LSD1), the first identified histone demethylase in 2004, existed in the cell cultured medium of gastric cancer cells. Further investigation confirmed the presence of LSD1 in sEVs from gastric cancer cells and gastric cancer patient plasma, which is the first identified histone demethylase in sEVs. By shuttling from donor cells to recipient gastric cancer cells, sEVs-delivered LSD1 promoted the cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2 and CD44, and suppressed the oxaliplatin response of the recipient cells in vitro and in vivo, while LSD1 depleted sEVs failed to suppress the oxaliplatin response. Collectively, our findings give an evidence for LSD1 as a sEVs protein to promote stemness and suppress oxaliplatin response for the first time and constitute a future avenue to predict oxaliplatin response in gastric cancer clinically.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Martin Pabst  

LAB HEAD: Dr Martin Pabst

PROVIDER: PXD020223 | Pride | 2021-12-22

REPOSITORIES: Pride