VC-resist glioblastoma cell state: vessel co-option as a key driver of chemoradiation resistance.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 Apr 2024
29 Apr 2024
Historique:
received:
10
11
2023
accepted:
17
04
2024
medline:
30
4
2024
pubmed:
30
4
2024
entrez:
29
4
2024
Statut:
epublish
Résumé
Glioblastoma (GBM) is a highly lethal type of cancer. GBM recurrence following chemoradiation is typically attributed to the regrowth of invasive and resistant cells. Therefore, there is a pressing need to gain a deeper understanding of the mechanisms underlying GBM resistance to chemoradiation and its ability to infiltrate. Using a combination of transcriptomic, proteomic, and phosphoproteomic analyses, longitudinal imaging, organotypic cultures, functional assays, animal studies, and clinical data analyses, we demonstrate that chemoradiation and brain vasculature induce cell transition to a functional state named VC-Resist (vessel co-opting and resistant cell state). This cell state is midway along the transcriptomic axis between proneural and mesenchymal GBM cells and is closer to the AC/MES1-like state. VC-Resist GBM cells are highly vessel co-opting, allowing significant infiltration into the surrounding brain tissue and homing to the perivascular niche, which in turn induces even more VC-Resist transition. The molecular and functional characteristics of this FGFR1-YAP1-dependent GBM cell state, including resistance to DNA damage, enrichment in the G2M phase, and induction of senescence/stemness pathways, contribute to its enhanced resistance to chemoradiation. These findings demonstrate how vessel co-option, perivascular niche, and GBM cell plasticity jointly drive resistance to therapy during GBM recurrence.
Identifiants
pubmed: 38684700
doi: 10.1038/s41467-024-47985-z
pii: 10.1038/s41467-024-47985-z
doi:
Substances chimiques
YAP-Signaling Proteins
0
YAP1 protein, human
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
3602Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 805225
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 805225
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 805225
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 805225
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2020-1-PLBIO-01-ICR-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2021-1-PAIR-CEREB-01-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2020-1-PLBIO-01-ICR-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2021-1-PAIR-CEREB-01-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2020-1-PLBIO-01-ICR-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2021-1-PAIR-CEREB-01-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2020-1-PLBIO-01-ICR-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2021-1-PAIR-CEREB-01-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2020-1-PLBIO-01-ICR-1
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-2021-1-PAIR-CEREB-01-1
Organisme : Centre National de la Recherche Scientifique (National Center for Scientific Research)
ID : ATIP-Avenir
Organisme : Université Paris-Saclay (University of Paris-Saclay)
ID : NanoTheRad
Informations de copyright
© 2024. The Author(s).
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