The chromatin remodeling BAP complex limits tumor promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation in<i>Drosophila</i>epithelia

Abstract

Switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are mutated in many human cancers. In this article, we make use of a <i>Drosophila</i> 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 (<i>Yki</i>) 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.