Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness.

Zhao LJ, Li YY, Zhang YT, Fan QQ, Ren HM, Zhang C, Mardinoglu A, Chen WC, Pang JR, Shen DD, Wang JW, Zhao LF, Zhang JY, Wang ZY, Zheng YC, Liu HM

EMBO Rep. 22 (8) e50922 [2021-08-04; online 2021-05-31]

Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.

Adil Mardinoglu

SciLifeLab Fellow

PubMed 34060205

DOI 10.15252/embr.202050922

Crossref 10.15252/embr.202050922

pmc: PMC8339672

Publications 9.5.0