Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles.
3-hydroxychloroquine
Autophagy
Autophagy modulation
Autophinib
Bafilomycin A1
CPD18
EACC
Extracellular vesicles
Head and neck cancer
NVP-BEZ235
Phosphatidylserine-positive extracellular vesicles
Proteomics
Rapamycin
SQSTM1
Senescence
Starvation
Torin1
p21
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
24 05 2023
24 05 2023
Historique:
received:
19
01
2023
accepted:
06
04
2023
medline:
26
5
2023
pubmed:
25
5
2023
entrez:
24
5
2023
Statut:
epublish
Résumé
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 TGFβ1 pro-protein. Interestingly, PS-EVs contained no commonly determined cytokines, such as IL-6, IL-8, GRO-α, 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. Video Abstract.
Identifiants
pubmed: 37226246
doi: 10.1186/s12964-023-01126-z
pii: 10.1186/s12964-023-01126-z
pmc: PMC10210466
doi:
Substances chimiques
Phosphatidylserines
0
Cytokines
0
Types de publication
Video-Audio Media
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
120Subventions
Organisme : Grant Agency of the Czech Republic
ID : GA21-06873S
Informations de copyright
© 2023. The Author(s).
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