A study of YAP/TAZ function in advanced breast cancer

Breast cancer (BC) is the leading type of cancer in women worldwide. Its lethality is mainly due to the development of aggressive therapy resistant metastases. The biological events involved in tumor initiation and progression have been widely investigated, however the mechanisms responsible for tumor maintenance remain still poorly understood. The elucidation of cellular events fueling tumor growth of established tumors is justified by the clinical need to have prognostic markers to divide breast cancer patients into “high risk” and “low risk” for disease relapse. Indeed, we lack exhaustive predictive markers of relapse and studying the signaling pathways active in established tumors can be the first step for the discovery of new predictive markers and novel therapeutic targets. From the multiple factors known to be important for BC initiation, YAP/TAZ transcriptional factors have a central role in breast cancer initiation. They are known for driving tumor and metastatic events in BC and their activation endows cancer cells with malignant features. Moreover, their high activity in human BC correlates with metastasis development and reduced patient survival. The aim of this PhD project is to investigate the role of YAP/TAZ in established breast tumors and the biological events involved in tumor progression. To do so, we developed BC experimental models to conditionally knockout (cKO) YAP/TAZ only in cancer cells and analyze the outcome in vivo. For deep investigation of the cellular processes triggered by YAP/TAZ cKO we used high resolution technologies such as single cell RNA sequencing and spatial transcriptomics.