Ectopic ATP synthase stimulates the secretion of extracellular vesicles in cancer cells
Journal
Communications biology
Journal Volume
6
Journal Issue
1
Pages
Article number 642
Date Issued
2023-06-15
Author(s)
Kao, Yi-Chun
Chang, Yi-Wen
Lai, Charles P
Chang, Nai-Wen
Huang, Chen-Hao
Chen, Chien-Sheng
Huang, Hsuan-Cheng
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.
SDGs
Publisher
Nature Research
Type
journal article