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XB-ART-60371
iScience 2023 Oct 20;2610:108075. doi: 10.1016/j.isci.2023.108075.
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Addition of exogenous diacylglycerol enhances Wnt/β-catenin signaling through stimulation of macropinocytosis.

Azbazdar Y , Tejeda-Munoz N , Monka JC , Dayrit A , Binder G , Ozhan G , De Robertis EM .


Abstract
Activation of Wnt signaling triggers macropinocytosis and drives many tumors. We now report that the exogenous addition of the second messenger lipid sn-1,2 DAG to the culture medium rapidly induces macropinocytosis. This is accompanied by potentiation of the effects of added Wnt3a recombinant protein or the glycogen synthase kinase 3 (GSK3) inhibitor lithium chloride (LiCl, which mimics Wnt signaling) in luciferase transcriptional reporter assays. In a colorectal carcinoma cell line in which mutation of adenomatous polyposis coli (APC) causes constitutive Wnt signaling, DAG addition increased levels of nuclear β-catenin, and this increase was partially inhibited by an inhibitor of macropinocytosis. DAG also expanded multivesicular bodies marked by the tetraspan protein CD63. In an in vivo situation, microinjection of DAG induced Wnt-like twinned body axes when co-injected with small amounts of LiCl into Xenopus embryos. These results suggest that the DAG second messenger plays a role in Wnt-driven cancer progression.

PubMed ID: 37860772
PMC ID: PMC10582480
Article link: iScience


Species referenced: Xenopus laevis
Genes referenced: axin1 calr cd63 lrp6 sox2 wnt3a
GO keywords: phosphatidylinositol-3,4,5-trisphosphate binding [+]


Article Images: [+] show captions
References [+] :
Albrecht, Cell Biology of Canonical Wnt Signaling. 2021, Pubmed