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Background: The wingless-type mammary tumour virus integration site 5A WNT5A agonist Foxy5 was shown in vitro to affect intracellular signalling implicated in the regulation of colonic cancer stem cells CSCs. Results: Foxy5 reduced the expression of the stem-cell marker aldehyde dehydrogenase and, interestingly, the specific colon CSC marker double cortin-like kinase 1. Foxy5 also reduced active β-catenin and the expression of its downstream target Achaete Scute complex homolog 2, a CSC-preserving transcription factor. Foxy5 also reduced cyclo-oxygenase 2 expression, responsible for the formation of the CSC-promoting prostaglandin E 2 PGE 2but increased that of hydroxyprostaglandin dehydrogenase expression, a PGE 2 -degrading enzyme. Accordingly, Foxy5 impairs both β-catenin and PGE 2 signalling, both of which have been implicated in promoting the niche of colonic CSCs.

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