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

• Main Authors: Shilin Song (Author), Héctor Herranz (Author), Stephen M. Cohen (Author)
• Format: Book
• Published: The Company of Biologists, 2017-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1754-8403; 1754-8411; 10.1242/dmm.030122
• Keywords: SWI/SNF; Hippo pathway; Yorkie; Oncogenic cooperation; Cancer; Drosophila; Medicine; R; Pathology; RB1-214
• Source: Disease Models & Mechanisms, Vol 10, Iss 10, Pp 1201-1209 (2017)

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.