Publication detail

Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles

HÁNĚLOVÁ, K. RAUDENSKÁ, M. KRATOCHVÍLOVÁ, M. NAVRÁTIL, J. VIČAR, T. BUGAJOVÁ, M. GUMULEC, J. MASAŘÍK, M. BALVAN, J.

Original Title

Type

journal article in Web of Science

Language

English

Original Abstract

Extracellular vesicles (EVs) are important mediators of intercellular communication in the tumour microenvironment. Many studies suggest that cancer cells release higher amounts of EVs exposing phosphatidylserine (PS) at the surface. There are lots of interconnections between EVs biogenesis and autophagy machinery. Modulation of autophagy can probably affect not only the quantity of EVs but also their content, which can deeply influence the resulting pro-tumourigenic or anticancer effect of autophagy modulators. In this study, we found that autophagy modulators autophinib, CPD18, EACC, bafilomycin A1 (BAFA1), 3-hydroxychloroquine (HCQ), rapamycin, NVP-BEZ235, Torin1, and starvation significantly alter the composition of the protein content of phosphatidylserine-positive EVs (PS-EVs) produced by cancer cells. The greatest impact had HCQ, BAFA1, CPD18, and starvation. The most abundant proteins in PS-EVs were proteins typical for extracellular exosomes, cytosol, cytoplasm, and cell surface involved in cell adhesion and angiogenesis. PS-EVs protein content involved mitochondrial proteins and signalling molecules such as SQSTM1 and TGF ss 1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-a, MCP-1, RANTES, and GM-CSF, which indicates that secretion of these cytokines is not predominantly mediated through PS-EVs. Nevertheless, the altered protein content of PS-EVs can still participate in the modulation of the fibroblast metabolism and phenotype as p21 was accumulated in fibroblasts influenced by EVs derived from CPD18-treated FaDu cells. The altered protein content of PS-EVs (data are available via ProteomeXchange with identifier PXD037164) also provides information about the cellular compartments and processes that are affected by the applied autophagy modulators.

Keywords

Extracellular vesicles; Phosphatidylserine-positive extracellular vesicles; Autophagy; Autophagy modulation; Head and neck cancer; Proteomics; SQSTM1; Senescence; p21; Autophinib; CPD18; EACC; Bafilomycin A1; 3-hydroxychloroquine; Rapamycin; NVP-BEZ235; Torin1; Starvation

Authors

HÁNĚLOVÁ, K.; RAUDENSKÁ, M.; KRATOCHVÍLOVÁ, M.; NAVRÁTIL, J.; VIČAR, T.; BUGAJOVÁ, M.; GUMULEC, J.; MASAŘÍK, M.; BALVAN, J.

Released

24. 5. 2023

Publisher

BMC

Location

LONDON

ISBN

1478-811X

Periodical

Cell Communication and Signaling

Year of study

Number

State

United Kingdom of Great Britain and Northern Ireland

Pages from

Pages to

Pages count

URL

https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01126-z

Full text in the Digital Library

http://hdl.handle.net/11012/213627

BibTex

@article{BUT183987,
  author="Klára {Hánělová} and Martina {Raudenská} and Monika {Kratochvílová} and Jiří {Navrátil} and Tomáš {Vičar} and Mária {Bugajová} and Jaromír {Gumulec} and Michal {Masařík} and Jan {Balvan}",
  title="Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles",
  journal="Cell Communication and Signaling",
  year="2023",
  volume="21",
  number="1",
  pages="1--21",
  doi="10.1186/s12964-023-01126-z",
  issn="1478-811X",
  url="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01126-z"
}