Expression of phosphorylated BRD4 is markedly associated with the activation status of the PP2A pathway and shows a strong prognostic value in triple negative breast cancer patients
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- dc.contributor.author Sanz Álvarez, Marta
- dc.contributor.author Cristóbal, Ion
- dc.contributor.author Luque, Melani
- dc.contributor.author Santos, Andrea
- dc.contributor.author Zazo, Sandra
- dc.contributor.author Madoz-Gúrpide, Juan
- dc.contributor.author Caramés, Cristina
- dc.contributor.author Chiang, Cheng-Ming
- dc.contributor.author García-Foncillas, Jesús
- dc.contributor.author Eroles, Pilar
- dc.contributor.author Albanell Mestres, Joan
- dc.contributor.author Rojo, Federico
- dc.date.accessioned 2021-09-06T06:58:44Z
- dc.date.available 2021-09-06T06:58:44Z
- dc.date.issued 2021
- dc.description.abstract The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. However, the potential clinical significance of pBRD4, as well as its potential correlation with the PP2A pathway in TNBC, remains to be investigated. Here, we evaluated the expression levels of pBRD4 in a series of 132 TNBC patients. We found high pBRD4 levels in 34.1% of cases (45/132), and this alteration was found to be associated with the development of patient recurrences (p = 0.007). Interestingly, BRD4 hyperphosphorylation predicted significantly shorter overall (p < 0.001) and event-free survival (p < 0.001). Moreover, multivariate analyses were performed to confirm its independent prognostic impact in our cohort. In conclusion, our findings show that BRD4 hyperphosphorylation is an alteration associated with PP2A inhibition that defines a subgroup of TNBC patients with unfavorable prognosis, suggesting the potential clinical and therapeutic usefulness of the PP2A/BRD4 axis as a novel molecular target to overcome resistance to treatments based on BRD4 inhibition.
- dc.format.mimetype application/pdf
- dc.identifier.citation Sanz-Álvarez M, Cristóbal I, Luque M, Santos A, Zazo S, Madoz-Gúrpide J, Caramés C, Chiang CM, García-Foncillas J, Eroles P, Albanell J, Rojo F. Expression of phosphorylated BRD4 is markedly associated with the activation status of the PP2A pathway and shows a strong prognostic value in triple negative breast cancer patients. Cancers (Basel). 2021;13(6):1246. DOI: 10.3390/cancers13061246
- dc.identifier.doi http://dx.doi.org/10.3390/cancers13061246
- dc.identifier.issn 2072-6694
- dc.identifier.uri http://hdl.handle.net/10230/48389
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof Cancers (Basel). 2021;13(6):1246
- dc.rights © 2021 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/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword PP2A
- dc.subject.keyword SET
- dc.subject.keyword pBRD4
- dc.subject.keyword Prognosis
- dc.subject.keyword Triple negative breast cancer
- dc.title Expression of phosphorylated BRD4 is markedly associated with the activation status of the PP2A pathway and shows a strong prognostic value in triple negative breast cancer patients
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion