PUBLICATION
The scaffolding protein Flot2 promotes cytoneme-based transport of Wnt3 in gastric cancer
- Authors
- Routledge, D., Rogers, S., Ono, Y., Brunt, L., Meniel, V., Tornillo, G., Ashktorab, H., Phesse, T., Scholpp, S.
- ID
- ZDB-PUB-220831-18
- Date
- 2022
- Source
- eLIFE 11: (Journal)
- Registered Authors
- Brunt, Lucy, Ono, Yosuke, Scholpp, Steffen
- Keywords
- cancer biology, cell biology, zebrafish
- MeSH Terms
-
- Animals
- Embryonic Development
- Stomach Neoplasms*
- Wnt Proteins/physiology
- Wnt Signaling Pathway
- Zebrafish*
- PubMed
- 36040316 Full text @ Elife
Citation
Routledge, D., Rogers, S., Ono, Y., Brunt, L., Meniel, V., Tornillo, G., Ashktorab, H., Phesse, T., Scholpp, S. (2022) The scaffolding protein Flot2 promotes cytoneme-based transport of Wnt3 in gastric cancer. eLIFE. 11:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping