Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.
breast cancer
extracellular vesicles
mitochondrial respiration
obesity
proliferation
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
revised:
19
10
2023
received:
13
04
2023
accepted:
20
10
2023
pmc-release:
06
11
2024
medline:
11
12
2023
pubmed:
6
11
2023
entrez:
6
11
2023
Statut:
ppublish
Résumé
Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. The mitochondrial complex I inhibitor metformin reverses O-EV-induced cell proliferation. Several miRNAs-miR-155-5p, miR-10a-3p, and miR-30a-3p-which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing metabolic reprogramming of breast cancer cells.
Identifiants
pubmed: 37929643
doi: 10.15252/embr.202357339
pmc: PMC10702795
doi:
Substances chimiques
Ribosomal Protein S6 Kinases, 70-kDa
EC 2.7.11.1
MicroRNAs
0
Proteins
0
Banques de données
GEO
['GSE245776']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57339Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215797
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023 The Authors.
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