The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling.

Journal Article (Journal Article)

Wnt proteins bind to seven-transmembrane Frizzled receptors to mediate the important developmental, morphogenetic, and stem cell related tissue-regenerative effects of Wnt signaling. Dysregulated Wnt signaling is associated with many cancers. Currently, there are no drug candidates or even tool compounds that modulate Wnt-mediated receptor trafficking, and subsequent Wnt signaling. We examined libraries of FDA-approved drugs for their utility as Frizzled internalization modulators, employing a primary imaged-based GFP fluorescence assay that uses Frizzled1 endocytosis as the readout. We now report that the anti-helminthic niclosamide, a drug used for the treatment of tapeworm, promotes Frizzled1 endocytosis, downregulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated beta-catenin stabilization and LEF/TCF reporter activity. Additionally, following niclosamide-mediated internalization, the Frizzled1 receptor colocalizes in vesicles containing transferrin and agonist-activated beta(2)-adrenergic receptor. Therefore, niclosamide may serve as a negative modulator of Wnt/Frizzled1 signaling by depleting upstream signaling molecules (i.e., Frizzled and Dishevelled) and moreover may provide a valuable means of studying the physiological consequences of Wnt signaling.

Full Text

Duke Authors

Cited Authors

  • Chen, M; Wang, J; Lu, J; Bond, MC; Ren, X-R; Lyerly, HK; Barak, LS; Chen, W

Published Date

  • November 3, 2009

Published In

Volume / Issue

  • 48 / 43

Start / End Page

  • 10267 - 10274

PubMed ID

  • 19772353

Pubmed Central ID

  • PMC2801776

Electronic International Standard Serial Number (EISSN)

  • 1520-4995

Digital Object Identifier (DOI)

  • 10.1021/bi9009677


  • eng

Conference Location

  • United States