API

Event: 1649

Key Event Title

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Snail, Zeb, Twist activation

Short name

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Snail, Zeb, Twist 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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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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•ZEB is one of the important transcription factors for EMT regulation (Zhang, Sun, & Ma, 2015).

•SNAI1 (Snail) is an important transcription factor for cell differentiation and survival, and the phosphorylation and nuclear localization of Snail1 induced by Wnt signaling pathways are critical for the regulation of EMT (Kaufhold & Bonavida, 2014).

•Transcription factors SNAI1 and TWIST1 induce EMT (Hodge, Cui, Gamble, & Guo, 2018) (Mani et al., 2008)

•It is suggested that Sp1, a transcription factor involved in cell growth and metastasis, is induced by cytochrome P450 1B1 (CYP1B1), and promotes EMT, which leads to cell proliferation and metastasis (Kwon et al., 2016).


How It Is Measured or Detected

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•The activation of Snail and Twist are measured with gene expression up-regulation by real-time PCR (Huang et al., 2019).

•ZEB1 and TWIST1 activation is measured by dual luciferase reporter assay detecting the promoter activation (Kwon et al., 2016)

•The protein expression of ZEB2, SNAI1 are measure by western blotting with antibodies (Kwon et al., 2016).


Domain of Applicability

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•Snail and Twist transcription factor is up-regulated in Homo sapiens (Huang et al., 2019).

•ZEB1 promoter activity is increased in Homo sapiens (Kwon et al., 2016).

•Twist1 is activated in Mus musculus (Laursen, Mielke, Iannaccone, & Fuchtbauer, 2007).


References

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Hodge, D. Q., Cui, J., Gamble, M. J., & Guo, W. (2018). Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing Epithelial-Mesenchymal Transition. Sci Rep, 8(1), 841. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29339820. doi:10.1038/s41598-018-19364-4

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

Kaufhold, S., & Bonavida, B. (2014). Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention. J Exp Clin Cancer Res, 33, 62. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25084828. doi:10.1186/s13046-014-0062-0

Kwon, Y. J., Baek, H. S., Ye, D. J., Shin, S., Kim, D., & Chun, Y. J. (2016). CYP1B1 Enhances Cell Proliferation and Metastasis through Induction of EMT and Activation of Wnt/beta-Catenin Signaling via Sp1 Upregulation. PLoS One, 11(3), e0151598. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26981862. doi:10.1371/journal.pone.0151598

Laursen, K. B., Mielke, E., Iannaccone, P., & Fuchtbauer, E. M. (2007). Mechanism of transcriptional activation by the proto-oncogene Twist1. J Biol Chem, 282(48), 34623-34633. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17893140. doi:10.1074/jbc.M707085200

Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., . . . Weinberg, R. A. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704-715. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18485877. doi:10.1016/j.cell.2008.03.027

Zhang, P., Sun, Y., & Ma, L. (2015). ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle, 14(4), 481-487. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/25607528. doi:10.1080/15384101.2015.1006048