Abstract 3055: Genome-wide CRISPR/Cas9 screen for the identification of novel YAP1/TAZ modulators

Aberrant activation of the Hippo pathway effectors YAP1/TAZ promotes cell proliferation and tumorigenesis. To identify novel regulators of YAP1/TAZ as a possible means to treat cancer, we established a novel, FACS-based screening system monitoring YAP1/TAZ activity in MDA-MB-231 breast cancer cells. Using these cells, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. We identified approximately 50 genes potentially activating YAP1/TAZ with functions in the Actin Cytoskeleton signaling, p53 signaling, cell polarity or ER stress, amongst others. Moreover, we identified about 30 potential targets which when knocked out induce activity of YAP1/TAZ. The list of hits included genes known to affect the YAP1/TAZ activity such as AJUBA, LATS2 and TEAD, demonstrating the validity of the screen. Functional validation of the novel potential YAP1/TAZ modulators will aid to the further understanding of YAP1/TAZ biology and may open the door to new therapeutic avenues for targeting YAP1/TAZ in cancer. Citation Format: Jan Naujoks, Lisette Potze, Anna Anurin, Julia Kuehnlenz, Ralf Lesche, Atanas Kamburov, Ekaterina Nevedomskaya, Andreas Steffen, Martin Lange, Barbara Nicke. Genome-wide CRISPR/Cas9 screen for the identification of novel YAP1/TAZ modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3055.