To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:1755
Event: 1755
Key Event Title
Proliferation / beta-catenin activation
Short name
Biological Context
Level of Biological Organization |
---|
Cellular |
Cell term
Cell term |
---|
cell |
Organ term
Organ term |
---|
organ |
Key Event Components
Process | Object | Action |
---|---|---|
regulation of beta-catenin-TCF complex assembly | beta-catenin-TCF complex | occurrence |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
Chronic ROS leading to human treatment-resistant gastric cancer | KeyEvent | Agnes Aggy (send email) | Open for comment. Do not cite | EAGMST Under Review |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Homo sapiens | Homo sapiens | High | NCBI |
Life Stages
Life stage | Evidence |
---|---|
All life stages | Moderate |
Sex Applicability
Term | Evidence |
---|---|
Unspecific | High |
Key Event Description
Upon the Wnt signaling activation, beta-catenin is stabilized and activated via inhibition of the phosphorylation by GSK3beta (Huang et al., 2019). Once the beta-catenin is stabilized, it translocates into the nucleus and enhances the expression of target genes of Wnt/beta-catenin signaling pathway (Huang et al., 2019). Beta-catenin activation is related to cancer (Tanabe, 2014).
Dishevelled (DVL), a positive regulator of Wnt signaling, forms the complex with FZD and leads to trigger the Wnt signaling together with Wnt coreceptor low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) (Clevers & Nusse, 2012; Jiang, et al., 2015). DVL, however, has a controversial role to promote Wnt receptor degradation (Jiang et al., 2015). Meanwhile, DVL-dependent regulation of FZD level is involved in mTORC1 signaling suppression via Wnt/beta-catenin signaling (Zeng et al., 2018). The recruitment of Axin to the DVL-FZD complex induces the beta-catenin stabilization and activation. The stabilized beta-catenin translocates into the nucleus, which forms the complex with TCF to induce the up-regulated expression of proliferation-related genes.
How It Is Measured or Detected
The beta-catenin level in nucleus is measured by immunoblotting with anti-beta-catenin antibody (Huang et al., 2019).
The beta-catenin nuclear translocation is measured by immunofluorescence assay (Huang et al., 2019).
Activity of beta-catenin is measured by Wnt/beta-catenin activity assay, in which the vector containing the firefly luciferase gene controlled by TCF/LEF binding sites is transfected in the cells (Naujok et al., 2014).
Domain of Applicability
Beta-catenin is stabilized and translocated into nucleus in Homo sapiens (Huang et al., 2019).
Beta-catenin is activated in Homo sapiens (Huang et al., 2019) (Naujok et al., 2014).
References
Clevers, H., & Nusse, R. (2012). Wnt/beta-catenin signaling and disease. Cell, 149(6), 1192-1205. doi:10.1016/j.cell.2012.05.012
Huang, J. Q., Wei, F. K., Xu, X. L., Ye, S. X., Song, J. W., Ding, P. K., . . . Gong, L. Y. (2019). SOX9 drives the epithelial-mesenchymal transition in non-small-cell lung cancer through the Wnt/beta-catenin pathway. J Transl Med, 17(1), 143. doi:10.1186/s12967-019-1895-2
Jiang, X., Charlat, O., Zamponi, R., Yang, Y., & Cong, F. (2015). Dishevelled promotes Wnt receptor degradation through recruitment of ZNRF3/RNF43 E3 ubiquitin ligases. Mol Cell, 58(3), 522-533. doi:10.1016/j.molcel.2015.03.015
Naujok, O., Lentes, J., Diekmann, U., Davenport, C., & Lenzen, S. (2014). Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors. BMC Res Notes, 7, 273. doi:10.1186/1756-0500-7-273
Tanabe, S. (2014). Role of mesenchymal stem cells in cell life and their signaling. World journal of stem cells, 6(1), 24-32. doi:10.4252/wjsc.v6.i1.24
Zeng, H., Lu, B., Zamponi, R., Yang, Z., Wetzel, K., Loureiro, J., . . . Cong, F. (2018). mTORC1 signaling suppresses Wnt/beta-catenin signaling through DVL-dependent regulation of Wnt receptor FZD level. Proc Natl Acad Sci U S A, 115(44), E10362-E10369. doi:10.1073/pnas.1808575115