The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia
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- The chromatin remodeling BAP complex limits tumor-promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in Drosophila epithelia
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Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing epidermal growth factor receptor (EGFR). The Brahma-associated protein (BAP) complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects. We provide evidence that BAP complex depletion causes upregulation of the Wingless (Wg) and Decapentaplegic (Dpp) morphogens to promote tumor formation in cooperation with Yki.
|Tidsskrift||Disease Models & Mechanisms|
|Status||Udgivet - 2017|
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