Functional Role of the YAP/TAZ antagonist Trps1 in the mammary gland

• Applicant: Dr. Björn von Eyss
• Subject Area: Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456324919

Breast cancer is one of the most common forms of cancer in the world and every year more than one million people worldwide are diagnosed with this type of tumor. Breast cancer originates from the two main cell types of the mammary gland: the basal and luminal cells. It is known that defects in the cell identity of these two cell types represent an early stage of tumor development, so these defects occur before the tumor is established. Consequently, the molecular understanding of these differentiation processes will provide us with a more accurate picture of the development of breast cancer tumors.Previous studies have shown that YAP/TAZ, as the co-activators of the Hippo pathway, can permanently reprogram the differentiation of breast epithelial cells towards the basal line. Our laboratory has recently identified the transcriptional repressor tricho-rhino-phalangeal syndrome 1 (Trps1) as a new negative regulator of YAP/TAZ activity in breast cancer cells. Trps1 represses the activity of YAP/TAZ by binding to the same genomic sites as YAP/TAZ and reducing their activity by recruiting co-pressors.Our laboratory has now developed a Trps1 shRNA mouse model that allows us to eliminate Trps1 expression in the adult mouse in a reversible manner. With this novel mouse line, we will be able to investigate the effects on the differentiation potential of the mammary gland after Trps1 loss and the effect on YAP/TAZ activity and address if a transient Trps1 depletion is able to reprogram cells similar to transient YAP/TAZ induction. Through a combination of various in vivo experiments - such as linear tracing - and state-of-the-art NGS-based methods (scRNA-Seq, ATAC-Seq, etc.) we will elucidate the exact molecular function of Trps1 in the mammary gland.With our work we hope to gain a better molecular understanding of the differentiation processes in the mammary gland and thus important insights into malfunctions of these processes, which pave the way for tumor development.

• DFG Programme: Research Grants