Role of mechanotransducers in breast cancer

YAP and TAZ are two transcriptional co-factors playing pivotal roles in a wide range of physiological processes, such as cell proliferation, survival, differentiation, tissue regeneration, and organ size determination. Interestingly, YAP and TAZ have been demonstrated to play a crucial role in endowing cancer cells with cancer stem cell features and in positively regulating proliferation, metastasis as well as chemoresistance. Moreover, their activation correlates with the grade, metastasis tendency, and resistance to therapies in Her2-positive and triple-negative breast cancer. Specifically, this thesis work deals with the generation of either YAP or TAZ knocked-out murine mammary carcinoma cell lines which can be then injected into a syngeneic mouse model for the evaluation of the role of these two genes in the primary tumor growth and lung metastases initiation, through a fat pad or tail vein injection, respectively. This approach is allowing us to study both the cell-autonomous effects of the deletion of these genes but also the potential non-cell-autonomous one, namely the role of YAP/TAZ in immune surveillance. These cells can be also used as a starting platform, with some modifications, for the study of mechanotransduction also in the maintenance of metastatic lesions.