Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jul;40(7):577-94.
doi: 10.1111/j.1745-7270.2008.00440.x.

Wnt signaling: the good and the bad

Affiliations

Wnt signaling: the good and the bad

Xi Chen et al. Acta Biochim Biophys Sin (Shanghai). 2008 Jul.

Abstract

Since the first Wnt gene was identified in 1982, the functions and mechanisms of Wnt signaling have been extensively studied. Wnt signaling is conserved from invertebrates to vertebrates and regulates early embryonic development as well as the homeostasis of adult tissues. In addition, both embryonic stem cells and adult stem cells are regulated by Wnt signaling. Deregulation of Wnt signaling is associated with many human diseases, particularly cancers. In this review, we will discuss in detail the functions of many components involved in the Wnt signal transduction pathway. Then, we will explore what is known about the role of Wnt signaling in stem cells and cancers.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. Secretion of Wnt proteins
Wnt is synthesized by ribosomes and acylated by Porcupine (Porc) in the ER. Wnt is then transferred to the Golgi. Wntless (WIS) helps transfer Wnt to endosomes, which then fuse with the cell membrane and Wnt is released outside of the cell. However, the secretion of Drosophila WntD does not require lipid modification.
Fig. 2
Fig. 2. Wnt signaling transduction pathway
(A) When Wnt signaling is “turned off”, cytoplasmic β-catenin is degraded by the Axin complex consisting of APC, GSK3 and CKIα. Within this complex, CKIα and GSK3 phosphorylate β-catenin, phosphorylated β-catenin is recognized by β-Trcp and degraded via the ubiquitination-proteasome pathway. Wnt protein can be inhibited by sFRPs, and LRP5/6 can be inhibited by DKK1. (B) When Wnt signaling is “turned on”, Wnt protein binds its receptor Frizzled and co-receptor LRP5/6 and stimulates LRP5/6 phosphorylation with the help of Dishevelled. Phosphorylated LRP5/6 recruits Axin to the membrane and disrupts the Axin complex. β-catenin accumulates in the cytoplasm and enters nucleus, where it binds TCF/LEF and co-activators, such as pygopus, legless and CBP/p300, and activates gene expression.
Fig. 3
Fig. 3
Structure of the intestine (A) and differentiation of intestinal stem cell (B)

Similar articles

Cited by

References

    1. Clevers H. Wnt/β-catenin signaling in development and disease. Cell. 2006;127:469–480. - PubMed
    1. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810. - PubMed
    1. Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31:99–109. - PubMed
    1. Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980;287:795–801. - PubMed
    1. McMahon AP, Moon RT. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell. 1989;58:1075–1084. - PubMed

Publication types