API

Event: 1648

Key Event Title

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β-catenin activation

Short name

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β-catenin activation

Biological Context

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Level of Biological Organization
Molecular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action

Key Event Overview

AOPs Including This Key Event

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AOP Name Role of event in AOP
Wnt activation leading to cancer malignancy KeyEvent

Stressors

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Name
CHIR-99021
CHIR-98014

Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages

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Life stage Evidence
All life stages High

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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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 enhance the expression of target genes of Wnt/beta-catenin signaling pathway (Huang et al., 2019). Beta-catenin activation is related to cancer(Tanabe, 2014).


How It Is Measured or Detected

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•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

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•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).


Evidence for Perturbation by Stressor


CHIR-99021

CHIR-99021 activates beta-catenin (Naujok et al., 2014).


CHIR-98014

CHIR-98014 activates beta-catenin (Naujok et al., 2014).


References

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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. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31060551. doi:10.1186/s12967-019-1895-2

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. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24779365. 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. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24567785

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927011/. doi:10.4252/wjsc.v6.i1.24