Abstract B41: Role of AIB1 in YAP-TEAD signaling in the progression of early-stage breast cancer

• Published in: Molecular cancer research 2020-08, Vol.18 (8_Supplement), p.B41-B41
• Main Authors: Kushner, Max Harley, Graham, Garrett, Sharif, Ghada, Kietzman, Will, Glasgow, Eric, Sangupta, Surojeet, Wellstein, Anton, Riegel, Anna Tate
• Format: Article
• Language: English
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1557-3125.HIPPO19-B41

AIB1 is an oncogenic transcription coactivator that is overexpressed and amplified in breast cancer and is known to interact with TEAD. AIB1, like YAP, is critical to the development and progression of triple-negative breast cancer, yet it is unclear to what extent the AIB1-TEAD interaction promotes the progression of triple-negative breast cancer. Herein, we confirm by ChIP and ChIP-seq that AIB1 is recruited to the chromatin with TEAD in complex with the YAP oncogene. In doing so, AIB1 potentiates YAP activity on a subset of TEAD target genes known to be critical to driving epithelial-to-mesenchymal and invasive behaviors in early-stage and advanced triple-negative breast cancer. Loss of AIB1 reverts the oncogenic phenotype conferred by YAP and attenuates 3D matrix invasion, migration, and endothelial extravasation, suggesting AIB1 may act as an oncogene in triple-negative breast cancer through YAP-TEAD. We find AIB1-YAP coregulation of a subset of oncogenic target genes that is determined by relative enrichment and global proximity of Oct1/POU2F1 binding motifs within target promoters. Thus, AIB1 is critical to maintaining YAP driven EMT and invasive phenotypes during the development and progression of triple-negative breast cancer. Citation Format: Max Harley Kushner, Garrett Graham, Ghada Sharif, Will Kietzman, Eric Glasgow, Surojeet Sangupta, Anton Wellstein, Anna Tate Riegel. Role of AIB1 in YAP-TEAD signaling in the progression of early-stage breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B41.