Elucidating the roles of YAP/TAZ in malignant vs. non-malignant cells in breast cancer

• Applicant: Dr. Björn von Eyss
• Subject Area: Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560415212

The Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also called TAZ) coactivators are the critical downstream transducers of the Hippo pathway, and they play a remarkable role in tissue regeneration and cancer development. However, the role of YAP/TAZ in cancer is very complex, as they can act as tumor suppressors in breast cancer, as high YAP/TAZ activity in breast cancer cells induces a strong immune response leading to tumor cell elimination. In addition, however, YAP/TAZ also play an important role in other (non-cancerous) cells of the breast tumor. For example, they are critically required for the formation of cancer-associated fibroblasts (CAFs) which help the tumor to evade immunosurveillance. Thus, it is up to now unresolved which of the different activities (oncogenic vs. tumor-suppressive) would prevail if YAP/TAZ would be inhibited in the whole body, e.g., using a drug. To address this question, we now generated mouse models which will allow us to interfere with YAP/TAZ function in the whole organism and all cells within a breast tumor (malignant and non-malignant). Ultimately, we aim to decipher whether YAP/TAZ can be used as a target for (breast) cancer therapies and which target cells would determine the outcome of a therapy.

• DFG Programme: Research Grants