Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer

北极光(Bora)可促进 Aurora A 激活 Plk1,在卵巢癌中具有致癌作用

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作者:Alfonso Parrilla, Marta Barber, Blanca Majem, Josep Castellví, Juan Morote, José Luis Sánchez, Asunción Pérez-Benavente, Miguel F Segura, Antonio Gil-Moreno, Anna Santamaria

Abstract

Identifying novel actionable factors that critically contribute to tumorigenesis is essential in ovarian cancer, an aggressive and disseminative tumor, with limited therapeutic options available. Here we show that Aurora Borealis (BORA), a mitotic protein that plays a key role in activating the master mitotic kinase polo-like kinase 1 (PLK1), has an oncogenic role in ovarian cancer. Gain and loss of function assays on mouse models and ex vivo patient-derived ascites cultures revealed an oncogenic role of BORA in tumor development and a transcriptome-analysis in clinically representative models depicted BORA's role in survival, dissemination and inflammatory cancer related-pathways. Importantly, combinatory treatments of FDA-approved inhibitors against oncogenic downstream effectors of BORA displayed synergistic effect in ovarian cancer models, offering promising therapeutic value. Altogether, our findings uncovered for the first time a critical role of BORA in the viability of human cancer cells providing potential novel therapeutic opportunities for ovarian cancer management.

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