GAP43-dependent mitochondria transfer from astrocytes enhances glioblastoma tumorigenicity.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
14
12
2022
accepted:
06
04
2023
medline:
29
5
2023
pubmed:
12
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor. We identified horizontal mitochondria transfer from astrocytes as a mechanism that enhances tumorigenesis in GBM. This transfer is dependent on network-forming intercellular connections between GBM cells and astrocytes, which are facilitated by growth-associated protein 43 (GAP43), a protein involved in neuron axon regeneration and astrocyte reactivity. The acquisition of astrocyte mitochondria drives an increase in mitochondrial respiration and upregulation of metabolic pathways linked to proliferation and tumorigenicity. Functionally, uptake of astrocyte mitochondria promotes cell cycle progression to proliferative G2/M phases and enhances self-renewal and tumorigenicity of GBM. Collectively, our findings reveal a host-tumor interaction that drives proliferation and self-renewal of cancer cells, providing opportunities for therapeutic development.
Identifiants
pubmed: 37169842
doi: 10.1038/s43018-023-00556-5
pii: 10.1038/s43018-023-00556-5
pmc: PMC10212766
doi:
Substances chimiques
GAP-43 Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
648-664Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA264849
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR002549
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA260735
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS127083
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007024
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA250254
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA253768
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA248611
Pays : United States
Organisme : NIH HHS
ID : S10 OD019972
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA234416
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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