Abstract 2308: The protein interaction landscape of breast cancer

Abstract Cancers have been associated with a diverse array of genomic alterations, many of which are rare with unknown significance. To understand the cellular mechanisms impacted by such alterations in breast invasive carcinoma, we have applied affinity-purification mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer proteins across three human breast cell lines, providing a novel resource of context-specific and shared protein-protein interaction networks in breast cancer cells. These networks interconnect and enrich for common and rare cancer mutations, and are substantially rewired by mutations. Our analysis identifies novel PIK3CA-interacting proteins which repress AKT signaling, and UBE2N emerges as a BRCA1 interactor predictive of clinical response to PARP inhibition. We also show that Spinophilin interacts with and dephosphorylates BRCA1 to promote DNA double-strand break repair. Thus, cancer protein interaction landscapes provide a framework for recognizing oncogenic drivers and drug vulnerabilities. Citation Format: Minkyu Kim, Jisoo Park, Mehdi Bouhaddou, Kyumin Kim, Ajda Rojc, Maya Modak, Margaret Soucheray, Patrick O'Leary, Denise Wolf, Dominique C. Mitchell, Fan Zheng, John D. Gordan, Jean-Philippe Coppé, Danielle L. Swaney, Laura van' t Veer, Alan Ashworth, Trey Ideker, Nevan J. Krogan. The protein interaction landscape of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2308.