2. Academic Validation
  3. Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness

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

  • EMBO Rep. 2021 Aug 4;22(8):e50922. doi: 10.15252/embr.202050922.
Li-Juan Zhao 1,  Ying-Ying Li 1,  Yu-Tong Zhang 1,  Qi-Qi Fan 1,  Hong-Mei Ren 1,  Cheng Zhang 2,  Adil Mardinoglu 2 3,  Wen-Chao Chen 4,  Jing-Ru Pang 1,  Dan-Dan Shen 1,  Jun-Wei Wang 1,  Long-Fei Zhao 1,  Jian-Ying Zhang 5,  Zhen-Ya Wang 6,  Yi-Chao Zheng 1,  Hong-Min Liu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
  • 2 Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.
  • 3 Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Host-Microbiome Interactions, King's College London, London, UK.
  • 4 Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
  • 5 Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
  • 6 Key Laboratory of "Runliang" Antiviral Medicines Research and Development, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, China.
PMID: 34060205 DOI: 10.15252/embr.202050922
Abstract

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.

Keywords

LSD1; gastric cancer; small extracellular vesicles; stemness.

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