Ricerc@Sapienza

Notch signaling is frequently activated in Ovarian Cancer (OC) and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. Several studies demonstrate that Notch3 expression renders cancer cells more resistant to carboplatin, contributing to chemoresistance and poor overall survival of OC patients. In addition, the activation of Notch3 is also associated with potential progression of ovarian cancer, tumor invasion and metastasis, which is of high relevance in OC as most patients experience disease recurrence. In this scenario, the Epithelial-mesenchymal transition (EMT) process needs to be considered, as the acquisition of the EMT phenotype is associated with drug resistance, and Notch3 significantly interferes with the EMT regulation and the metastatic capacity of malignant cells.
This suggests that Notch3 can represent both a prognostic marker and a therapeutic target for the treatment of OC patients. However, the underlying molecular mechanisms of Notch3 activity are not yet very clear. Here, we aim to explore in details the crucial role of Notch3 in ovarian cancer metastasis and chemotherapy resistance, focusing our attention on its protein function and regulation through the involvement of the cis-trans isomerase Pin1, known to regulate the Notch3 protein via a phopshorylation-dependent mechanism. Collectively, our findings will allow us to provide novel therapeutic approaches for ovarian cancer treatment, thus improving OC patients outcome.