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

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 mast...

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Autores principales: Parrilla, Alfonso, Barber, Marta, Majem, Blanca, Castellví, Josep, Morote, Juan, Sánchez, José Luis, Pérez-Benavente, Asunción, Segura, Miguel F., Gil-Moreno, Antonio, Santamaria, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226261/
https://www.ncbi.nlm.nih.gov/pubmed/32268485
http://dx.doi.org/10.3390/cancers12040886
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author Parrilla, Alfonso
Barber, Marta
Majem, Blanca
Castellví, Josep
Morote, Juan
Sánchez, José Luis
Pérez-Benavente, Asunción
Segura, Miguel F.
Gil-Moreno, Antonio
Santamaria, Anna
author_facet Parrilla, Alfonso
Barber, Marta
Majem, Blanca
Castellví, Josep
Morote, Juan
Sánchez, José Luis
Pérez-Benavente, Asunción
Segura, Miguel F.
Gil-Moreno, Antonio
Santamaria, Anna
author_sort Parrilla, Alfonso
collection PubMed
description 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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spelling pubmed-72262612020-05-18 Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer Parrilla, Alfonso Barber, Marta Majem, Blanca Castellví, Josep Morote, Juan Sánchez, José Luis Pérez-Benavente, Asunción Segura, Miguel F. Gil-Moreno, Antonio Santamaria, Anna Cancers (Basel) Article 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. MDPI 2020-04-06 /pmc/articles/PMC7226261/ /pubmed/32268485 http://dx.doi.org/10.3390/cancers12040886 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parrilla, Alfonso
Barber, Marta
Majem, Blanca
Castellví, Josep
Morote, Juan
Sánchez, José Luis
Pérez-Benavente, Asunción
Segura, Miguel F.
Gil-Moreno, Antonio
Santamaria, Anna
Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title_full Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title_fullStr Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title_full_unstemmed Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title_short Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer
title_sort aurora borealis (bora), which promotes plk1 activation by aurora a, has an oncogenic role in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226261/
https://www.ncbi.nlm.nih.gov/pubmed/32268485
http://dx.doi.org/10.3390/cancers12040886
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