The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer.
Wnt
cancer biology
cell biology
cytoneme
gastric cancer
lipid rafts
plasma membrane
signalling
zebrafish
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
30 08 2022
30 08 2022
Historique:
received:
26
01
2022
accepted:
27
08
2022
pubmed:
31
8
2022
medline:
14
9
2022
entrez:
30
8
2022
Statut:
epublish
Résumé
The Wnt/β-catenin signalling pathway regulates multiple cellular processes during development and many diseases, including cell proliferation, migration, and differentiation. Despite their hydrophobic nature, Wnt proteins exert their function over long distances to induce paracrine signalling. Recent studies have identified several factors involved in Wnt secretion; however, our understanding of how Wnt ligands are transported between cells to interact with their cognate receptors is still debated. Here, we demonstrate that gastric cancer cells utilise cytonemes to transport Wnt3 intercellularly to promote proliferation and cell survival. Furthermore, we identify the membrane-bound scaffolding protein Flotillin-2 (Flot2), frequently overexpressed in gastric cancer, as a modulator of these cytonemes. Together with the Wnt co-receptor and cytoneme initiator Ror2, Flot2 determines the number and length of Wnt3 cytonemes in gastric cancer. Finally, we show that Flotillins are also necessary for Wnt8a cytonemes during zebrafish embryogenesis, suggesting a conserved mechanism for Flotillin-mediated Wnt transport on cytonemes in development and disease.
Identifiants
pubmed: 36040316
doi: 10.7554/eLife.77376
pii: 77376
pmc: PMC9457691
doi:
pii:
Substances chimiques
Wnt Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/R026424/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S016295/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S007970/1
Pays : United Kingdom
Organisme : NIMHD NIH HHS
ID : U54 MD007597
Pays : United States
Organisme : Medical Research Council
ID : MR/N0137941/1
Pays : United Kingdom
Informations de copyright
© 2022, Routledge et al.
Déclaration de conflit d'intérêts
DR, SR, YO, LB, VM, GT, HA, TP, SS No competing interests declared
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