2. Academic Validation
  3. Ectopic ATP synthase stimulates the secretion of extracellular vesicles in cancer cells

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

  • Commun Biol. 2023 Jun 15;6(1):642. doi: 10.1038/s42003-023-05008-5.
Yi-Chun Kao 1,  Yi-Wen Chang 1,  Charles P Lai 2,  Nai-Wen Chang 3,  Chen-Hao Huang 4,  Chien-Sheng Chen 5,  Hsuan-Cheng Huang 6,  Hsueh-Fen Juan 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Life Science, National Taiwan University, Taipei, 106, Taiwan.
  • 2 Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106, Taiwan.
  • 3 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106, Taiwan.
  • 4 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 106, Taiwan.
  • 5 Department of Food Safety / Hygiene and Risk Management, National Cheng Kung University, Tainan, Taiwan.
  • 6 Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan. [email protected].
  • 7 Department of Life Science, National Taiwan University, Taipei, 106, Taiwan. [email protected].
  • 8 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, 106, Taiwan. [email protected].
  • 9 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 106, Taiwan. [email protected].
  • 10 Center for Computational and Systems Biology, National Taiwan University, Taipei, 106, Taiwan. [email protected].
PMID: 37322056 DOI: 10.1038/s42003-023-05008-5
Abstract

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 P2X7 receptor-triggered Ca2+ 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.

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