A complex of Wnt/planar cell polarity signaling components Vangl1 and Fzd7 drives glioblastoma multiforme malignant properties.
Glioblastoma
Motility
Noncanonical Wnt signaling
Planar cell polarity
Proliferation
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 07 2023
28 07 2023
Historique:
received:
15
03
2023
revised:
09
06
2023
accepted:
12
06
2023
pmc-release:
28
07
2024
medline:
4
7
2023
pubmed:
20
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
Targeting common oncogenic drivers of glioblastoma multiforme (GBM) in patients has remained largely ineffective, raising the possibility that alternative pathways may contribute to tumor aggressiveness. Here we demonstrate that Vangl1 and Fzd7, components of the non-canonical Wnt planar cell polarity (Wnt/PCP) signaling pathway, promote GBM malignancy by driving cellular proliferation, migration, and invasiveness, and engage Rho GTPases to promote cytoskeletal rearrangements and actin dynamics in migrating GBM cells. Mechanistically, we uncover the existence of a novel Vangl1/Fzd7 complex at the leading edge of migrating GBM cells and propose that this complex is critical for the recruitment of downstream effectors to promote tumor progression. Moreover, we observe that depletion of FZD7 results in a striking suppression of tumor growth and latency and extends overall survival in an intracranial mouse xenograft model. Our observations support a novel mechanism by which Wnt/PCP components Vangl1 and Fzd7 form a complex at the leading edge of migratory GBM cells to engage downstream effectors that promote actin cytoskeletal rearrangements dynamics. Our findings suggest that interference with Wnt/PCP pathway function may offer a novel therapeutic strategy for patients diagnosed with GBM.
Identifiants
pubmed: 37336284
pii: S0304-3835(23)00231-8
doi: 10.1016/j.canlet.2023.216280
pmc: PMC10582999
mid: NIHMS1935936
pii:
doi:
Substances chimiques
Actins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
216280Subventions
Organisme : NCI NIH HHS
ID : R01 CA230742
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA246900
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA210467
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL152621
Pays : United States
Organisme : NICHD NIH HHS
ID : DP2 HD094656
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing interests.
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