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SOX7 Suppresses Wnt Signaling by Disrupting β-Catenin/BCL9 Interaction
Rong Fan1, HaiYan He2, Wang Yao1
11 Department of Cardiology, Yueyang Hospital Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine , Shanghai, China .
Abstract:
The Wnt signaling is involved in angiogenesis and tumor development. β-catenin is the core component of the Wnt pathway, which mediates oncogenic transcription and regulated by a series of proteins. Sex-determining region Y-box 7 (SOX7) is a member of high-mobility-group transcription factor family, which inhibits oncogenic Wnt signaling in lots of tumor cells with unknown mechanism. By coimmunoprecipitation (co-IP) and super Topflash reporter assay, SOX7 can bind β-catenin and inhibit β-catenin/T cell factor (TCF)-mediated transcription. Meanwhile, B cell lymphoma 9 (BCL9) drives Wnt signaling path through direct binding-mediated β-catenin. Finally, we found that SOX7 inhibits oncogenic β-catenin-mediated transcription by disrupting the β-catenin/BCL9 interaction. Mechanistically, SOX7 compete with BCL9 to bind β-catenin. Our results show SOX7 inhibited Wnt signaling as suppressor and could be an important target for anticancer therapy.
Insights
Sex-determining region Y-box 7 (SOX7) inhibits Wnt signaling, a pathway crucial for tumor development. SOX7 disrupts the interaction between β-catenin and BCL9, acting as a tumor suppressor and potential anticancer target.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Wnt signaling pathway is implicated in angiogenesis and tumor progression.
- β-catenin is a key mediator of oncogenic Wnt signaling.
- The precise mechanism by which SOX7 inhibits Wnt signaling in tumors is not fully understood.
Purpose of the Study:
- To elucidate the mechanism by which Sex-determining region Y-box 7 (SOX7) inhibits oncogenic Wnt signaling.
- To investigate the interaction between SOX7, β-catenin, and BCL9.
- To evaluate SOX7 as a potential therapeutic target for cancer.
Main Methods:
- Co-immunoprecipitation (co-IP) assays to assess protein interactions.
- Super Topflash reporter assays to measure Wnt/β-catenin transcriptional activity.
- Analysis of SOX7's effect on the β-catenin/BCL9 complex.
Main Results:
- SOX7 directly binds to β-catenin.
- SOX7 inhibits β-catenin/T cell factor (TCF)-mediated transcription.
- SOX7 disrupts the interaction between β-catenin and BCL9 by competing for β-catenin binding.
- SOX7 functions as a suppressor of oncogenic Wnt signaling.
Conclusions:
- SOX7 inhibits oncogenic Wnt signaling by preventing the β-catenin/BCL9 interaction.
- SOX7 acts as a tumor suppressor by targeting the Wnt pathway.
- SOX7 represents a promising therapeutic target for anticancer strategies.
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