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Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy
Citation
Taylor, J and Azimi, I and Monteith, G, Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy, Journal of Extracellular Vesicles, 9, (1) pp. 1-14. ISSN 2001-3078 (2020) [Refereed Article]
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Copyright Statement
Copyright 2020 The Authors. Licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/
DOI: doi:10.1080/20013078.2020.1734326
Abstract
Extracellular vesicles (EVs) are small extracellular membrane vesicles that serve as important intercellular signalling intermediaries in both malignant and non-malignant cells. For EVs formed by the
plasma membrane, their biogenesis is characterized by an increase in intracellular calcium followed
by successive membrane and cytoskeletal changes. EV production is significantly higher in malignant
cells relative to non-malignant cells and previous work suggests this is dependent on increased
calcium mobilization and activity of calpain. However, differences in calcium-signalling pathways in
the context of malignant and non-malignant EV biogenesis remain unexplored. Here, we demonstrate vesiculation is greater in malignant MCF-7 cells relative to non-malignant hCMEC-D3 cells,
increases in free cytosolic Ca2+via endoplasmic reticulum (ER) Ca2+ store depletion with thapsigargin
increases EV biogenesis in both cell types, and vesicular induction is abolished by the intracellular Ca2
+ chelator BAPTA-AM. Store-operated calcium entry (SOCE) plays an essential role in the maintenance
of EV biogenesis after store depletion. These findings contribute to furthering our understanding of
extracellular vesicle biogenesis. Furthermore, since EVs are key mediators in the intercellular transfer
of deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecular
mechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutic
targets that circumvent EV-mediated MDR.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Calcium, extracellular vesicle biogenesis, cancer |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Pharmacology and pharmaceutical sciences not elsewhere classified |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Azimi, I (Dr Iman Azimi) |
| ID Code: | 138070 |
| Year Published: | 2020 |
| Web of Science® Times Cited: | 32 |
| Deposited By: | Pharmacy |
| Deposited On: | 2020-03-24 |
| Last Modified: | 2021-10-28 |
| Downloads: | 15 View Download Statistics |
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