The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Routledge, Daniel, Rogers, Sally, Ono, Yosuke, Brunt, Lucy, Meniel, Valerie, Tornillo, Giusy, Ashktorab, Hassan, Phesse, Toby J ORCID: https://orcid.org/0000-0001-9568-4916 and Scholpp, Steffen 2022. The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife 11 , e77376. 10.7554/elife.77376

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/
Publisher:	eLife Sciences Publications
Date of First Compliant Deposit:	9 September 2022
Date of Acceptance:	27 August 2022
Last Modified:	11 Oct 2023 21:26
URI:	https://orca.cardiff.ac.uk/id/eprint/152442

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