API

Relationship: 2033

Title

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Increased, Reactive oxygen species leads to β-catenin activation

Upstream event

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Increased, Reactive oxygen species

Downstream event

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β-catenin activation

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens Moderate NCBI

Sex Applicability

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Sex Evidence
Unspecific High

Life Stage Applicability

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Term Evidence
All life stages Moderate

Key Event Relationship Description

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Reactive oxygen species (ROS) increase causes beta-catenin stabilization leading to the activation. RSO may activate beta-catenin by releasing the nucleoredoxin (NRX), a thioredoxin family protein, mediated block on Dishevelled (Dvl) activity which is importantt for beta-catenin stabilization [Korswagen, 2006, Funato, 2006].

Evidence Supporting this KER

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Biological Plausibility

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ROS which promotes the cancer progression induces several pathways including Wnt/beta-catenin pathway [Korswagen, 2006, Funato, 2006].

Empirical Evidence

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Lycopene, one of the major carotenoid natural products with antioxidant activity, induces apoptosis of gastric cancer cells by inhibiting nuclear translocation of beta-catenin [Kim, 20019]. ROS generated by arsenic mediates tumorigenesis through Wnt/beta-catenin pathway in which beta-catenin expression increases and activated [Zhang, 2011].

Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Funato, Y., Michiue, T., Asashima, M., & Miki, H. (2006). The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt–β-catenin signalling through Dishevelled. Nature Cell Biology, 8(5), 501-508. doi:10.1038/ncb1405

Korswagen, H. C. (2006). Regulation of the Wnt/β-catenin pathway by redox signaling. Developmental Cell, 10(6), 687-688.

Kim, M., Kim, S. H., Lim, J. W., & Kim, H. (2019). Lycopene induces apoptosis by inhibiting nuclear translocation of beta-catenin in gastric cancer cells. J Physiol Pharmacol, 70(4). doi:10.26402/jpp.2019.4.11

Zhang, Z., Wang, X., Cheng, S., Sun, L., Son, Y.-O., Yao, H., . . . Shi, X. (2011). Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells. Toxicology and Applied Pharmacology, 256(2), 114-121.