SOX7 Suppresses Wnt Signaling by Disrupting -Catenin/BCL9 Interaction

作者:Fan, Rong; He, HaiYan; Yao, Wang; Zhu, YanFeng; Zhou, XunJie; Gui, MingTai; Lu, Jing; Xi, Hao; Deng, ZhongLong; Fan, Min*
来源:DNA and Cell Biology, 2018, 37(2): 126-132.
DOI:10.1089/dna.2017.3866

摘要

The Wnt signaling is involved in angiogenesis and tumor development. -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 -catenin and inhibit -catenin/T cell factor (TCF)-mediated transcription. Meanwhile, B cell lymphoma 9 (BCL9) drives Wnt signaling path through direct binding-mediated -catenin. Finally, we found that SOX7 inhibits oncogenic -catenin-mediated transcription by disrupting the -catenin/BCL9 interaction. Mechanistically, SOX7 compete with BCL9 to bind -catenin. Our results show SOX7 inhibited Wnt signaling as suppressor and could be an important target for anticancer therapy.