PUBLICATION
Twa1/Gid8 is a β-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis
- Authors
- Lu, Y., Xie, S., Zhang, W., Zhang, C., Gao, C., Sun, Q., Cai, Y., Xu, Z., Xiao, M., Xu, Y., Huang, X., Wu, X., Liu, W., Wang, F., Kang, Y., Zhou, T.
- ID
- ZDB-PUB-170823-5
- Date
- 2017
- Source
- Cell Research 27(12): 1422-1440 (Journal)
- Registered Authors
- Wang, Fudi
- Keywords
- none
- MeSH Terms
-
- Mice
- beta Catenin/metabolism*
- Animals
- Computational Biology
- Wnt Signaling Pathway*
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Mice, Nude
- Neoplasms, Experimental/genetics
- Neoplasms, Experimental/metabolism
- Neoplasms, Experimental/pathology
- Colonic Neoplasms/genetics
- Colonic Neoplasms/metabolism*
- Colonic Neoplasms/pathology*
- Cell Nucleus/metabolism*
- Carcinogenesis*/genetics
- Carcinogenesis*/pathology
- Cells, Cultured
- Zebrafish
- Humans
- Female
- PubMed
- 28829046 Full text @ Cell Res.
Citation
Lu, Y., Xie, S., Zhang, W., Zhang, C., Gao, C., Sun, Q., Cai, Y., Xu, Z., Xiao, M., Xu, Y., Huang, X., Wu, X., Liu, W., Wang, F., Kang, Y., Zhou, T. (2017) Twa1/Gid8 is a β-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis. Cell Research. 27(12):1422-1440.
Abstract
Hyperactivation of Wnt/β-catenin signaling is one of the major causes of human colorectal cancer (CRC). A hallmark of Wnt signaling is the nuclear accumulation of β-catenin. Although β-catenin nuclear import and export have been widely investigated, the underlying mechanism of β-catenin's nuclear retention remains largely unknown. Here, we report that Twa1/Gid8 is a key nuclear retention factor for β-catenin during Wnt signaling and colorectal carcinogenesis. In the absence of Wnt, Twa1 exists together with β-catenin in the Axin complex and undergoes ubiquitination and degradation. Upon Wnt signaling, Twa1 translocates into the nucleus, where it binds and retains β-catenin. Depletion of Twa1 attenuates Wnt-stimulated gene expression, dorsal development of zebrafish embryos and xenograft tumor growth of CRC cells. Moreover, nuclear Twa1 is significantly upregulated in human CRC tissues, correlating with the nuclear accumulation of β-catenin and poor prognosis. Thus, our results identify Twa1 as a previously undescribed regulator of the Wnt pathway for promoting colorectal tumorigenesis by facilitating β-catenin nuclear retention.Cell Research advance online publication 22 August 2017; doi:10.1038/cr.2017.107.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping