Ectopic ATP synthase stimulates the secretion of extracellular vesicles in cancer cells.

Autor: Kao YC; Department of Life Science, National Taiwan University, Taipei, 106, Taiwan., Chang YW; Department of Life Science, National Taiwan University, Taipei, 106, Taiwan., Lai CP; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan., Chang NW; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106, Taiwan., Huang CH; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 106, Taiwan., Chen CS; Department of Food Safety / Hygiene and Risk Management, National Cheng Kung University, Tainan, Taiwan., Huang HC; Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan. hsuancheng@nycu.edu.tw., Juan HF; Department of Life Science, National Taiwan University, Taipei, 106, Taiwan. yukijuan@ntu.edu.tw.; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106, Taiwan. yukijuan@ntu.edu.tw.; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 106, Taiwan. yukijuan@ntu.edu.tw.; Center for Computational and Systems Biology, National Taiwan University, Taipei, 106, Taiwan. yukijuan@ntu.edu.tw.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Jun 15; Vol. 6 (1), pp. 642. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1038/s42003-023-05008-5
Abstrakt: Abstarct: Ectopic ATP synthase on the plasma membrane (eATP synthase) has been found in various cancer types and is a potential target for cancer therapy. However, whether it provides a functional role in tumor progression remains unclear. Here, quantitative proteomics reveals that cancer cells under starvation stress express higher eATP synthase and enhance the production of extracellular vesicles (EVs), which are vital regulators within the tumor microenvironment. Further results show that eATP synthase generates extracellular ATP to stimulate EV secretion by enhancing P2X 7 receptor-triggered Ca 2+ influx. Surprisingly, eATP synthase is also located on the surface of tumor-secreted EVs. The EVs-surface eATP synthase increases the uptake of tumor-secreted EVs in Jurkat T-cells via association with Fyn, a plasma membrane protein found in immune cells. The eATP synthase-coated EVs uptake subsequently represses the proliferation and cytokine secretion of Jurkat T-cells. This study clarifies the role of eATP synthase on EV secretion and its influence on immune cells.
(© 2023. The Author(s).)
Databáze: MEDLINE
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