» Articles » PMID: 23085770

Secreted and Transmembrane Wnt Inhibitors and Activators

Overview
Date 2012 Oct 23
PMID 23085770
Citations 330
Authors
Affiliations
Soon will be listed here.
Abstract

Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease.

Citing Articles

Reversal of chemotherapy resistance in gastric cancer with traditional Chinese medicine as sensitizer: potential mechanism of action.

Zhou C, Wu K, Gu M, Yang Y, Tu J, Huang X Front Oncol. 2025; 15:1524182.

PMID: 40052129 PMC: 11882405. DOI: 10.3389/fonc.2025.1524182.


Role of GPCR Signaling in Anthracycline-Induced Cardiotoxicity.

Biswal N, Harish R, Roshan M, Samudrala S, Jiao X, Pestell R Cells. 2025; 14(3).

PMID: 39936961 PMC: 11817789. DOI: 10.3390/cells14030169.


BRD4 Induces Esophageal Squamous Cell Carcinoma Progression via the Wnt/β-catenin Pathway.

Niu H, Wei H, Zhou X, Liu Y, Yang L, Wang Q Biochem Genet. 2025; .

PMID: 39903433 DOI: 10.1007/s10528-025-11043-0.


The co-receptor Tetraspanin12 directly captures Norrin to promote ligand-specific β-catenin signaling.

Bruguera E, Mahoney J, Weis W Elife. 2025; 13.

PMID: 39745873 PMC: 11695057. DOI: 10.7554/eLife.96743.


The Role of Wnt3a/β-Catenin/TCF7L2 Pathway in Diabetes and Cardiorenal Complications.

Adeerjiang Y, Sidike A, Gan X, Li Q, Jiang S Cardiorenal Med. 2024; 15(1):72-82.

PMID: 39709946 PMC: 11844670. DOI: 10.1159/000543145.


References
1.
Ahn Y, Sanderson B, Klein O, Krumlauf R . Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development. 2010; 137(19):3221-31. PMC: 6512258. DOI: 10.1242/dev.054668. View

2.
Stanley E, Biben C, Allison J, Hartley L, Wicks I, Campbell I . Targeted insertion of a lacZ reporter gene into the mouse Cer1 locus reveals complex and dynamic expression during embryogenesis. Genesis. 2000; 26(4):259-64. DOI: 10.1002/(sici)1526-968x(200004)26:4<259::aid-gene70>3.0.co;2-v. View

3.
Grotewold L, Ruther U . The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death. EMBO J. 2002; 21(5):966-75. PMC: 125884. DOI: 10.1093/emboj/21.5.966. View

4.
Staehling-Hampton K, Proll S, Paeper B, Zhao L, Charmley P, Brown A . A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet. 2002; 110(2):144-52. DOI: 10.1002/ajmg.10401. View

5.
Theodorou V, Kimm M, Boer M, Wessels L, Theelen W, Jonkers J . MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet. 2007; 39(6):759-69. DOI: 10.1038/ng2034. View