Glutamine and serum starvation alters the ATP production, oxidative stress, and abundance of mitochondrial RNAs in extracellular vesicles produced by cancer cells.
Humans
Extracellular Vesicles
/ metabolism
Oxidative Stress
Cell Line, Tumor
Adenosine Triphosphate
/ metabolism
Glutamine
/ metabolism
RNA, Mitochondrial
/ metabolism
Autophagy
/ drug effects
Mitochondria
/ metabolism
Squamous Cell Carcinoma of Head and Neck
/ metabolism
Head and Neck Neoplasms
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 10 2024
28 10 2024
Historique:
received:
15
04
2024
accepted:
23
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Induction of autophagy represents an effective survival strategy for nutrient-deprived or stressed cancer cells. Autophagy contributes to the modulation of communication within the tumor microenvironment. Here, we conducted a study of the metabolic and signaling implications associated with autophagy induced by glutamine (Gln) and serum starvation and PI3K/mTOR inhibitor and autophagy inducer NVP-BEZ235 (BEZ) in the head and neck squamous cell carcinoma (HNSCC) cell line FaDu. We compared the effect of these different types of autophagy induction on ATP production, lipid peroxidation, mitophagy, RNA cargo of extracellular vesicles (EVs), and EVs-associated cytokine secretome of cancer cells. Both BEZ and starvation resulted in a decline in ATP production. Simultaneously, Gln starvation enhanced oxidative damage of cancer cells by lipid peroxidation. In starved cells, there was a discernible fragmentation of the mitochondrial network coupled with an increase in the presence of tumor susceptibility gene 101 (TSG101) on the mitochondrial membrane, indicative of the sorting of mitochondrial cargo into EVs. Consequently, the abundance of mitochondrial RNAs (mtRNAs) in EVs released by FaDu cells was enhanced. Notably, mtRNAs were also detectable in EVs isolated from the serum of both HNSCC patients and healthy controls. Starvation and BEZ reduced the production of EVs by cancer cells, yet the characteristic molecular profile of these EVs remained unchanged. We also found that alterations in the release of inflammatory cytokines constitute a principal response to autophagy induction. Importantly, the specific mechanism driving autophagy induction significantly influenced the composition of the EVs-associated cytokine secretome.
Identifiants
pubmed: 39468126
doi: 10.1038/s41598-024-73943-2
pii: 10.1038/s41598-024-73943-2
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Glutamine
0RH81L854J
RNA, Mitochondrial
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25815Subventions
Organisme : Grantová Agentura České Republiky
ID : GACR-21-06873S
Organisme : Grantová Agentura České Republiky
ID : GACR-21-06873S
Organisme : Grantová Agentura České Republiky
ID : GACR-21-06873S
Organisme : Grantová Agentura České Republiky
ID : GACR-21-06873S
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Organisme : Ministerstvo Zdravotnictví Ceské Republiky
ID : NU20J-08-00018
Informations de copyright
© 2024. The Author(s).
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