Abstract 5434: Screen for immune-related transcriptional targets of the Hippo pathway in human breast cancer cells

The Hippo signaling pathway has recently emerged as a cellular network that is dysregulated in cancer. In breast cancer cells, aberrant activation of the Hippo transducers (and transcriptional co-activators) TAZ and YAP leads to altered expression of their downstream gene targets and endows cells with multiple “hallmarks of cancer”. While several transcriptional targets of TAZ and YAP underlying their pro-tumorigenic activity have been described (e.g. CTGF, CYR61), gene targets of TAZ and YAP that modulate immune cell behavior in the tumor microenvironment are poorly understood. We have performed a comprehensive screen for immune-related transcriptional targets of TAZ and YAP in human breast cells. We have identified many candidate genes that are potentially regulated by TAZ and YAP including the immune checkpoint molecules PD-L1 and PD-L2, the lymphocyte regulator S1PR1 and the inflammasome component NLRP3. We have further validated PD-L1 as a bona fide transcriptional target of TAZ and YAP. These findings reveal new functions for the Hippo pathway in modifying immune responses and implicate TAZ and YAP in cancer immune evasion. Citation Format: Helena J. Janse van Rensburg, Taha Azad, Min Ling, Yawei Hao, Lori M. Minassian, Brooke Snetsinger, Prem Khanal, Michael J. Rauh, Charles H. Graham, Xiaolong Yang. Screen for immune-related transcriptional targets of the Hippo pathway in human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5434.