CIP2A as a key regulator for AKT phosphorylation has partial impact determining clinical outcome in breast cancer

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• dc.contributor.author Luque, Melani
• dc.contributor.author Cristóbal, Ion
• dc.contributor.author Sanz Álvarez, Marta
• dc.contributor.author Santos, Andrea
• dc.contributor.author Zazo, Sandra
• dc.contributor.author Eroles, Pilar
• dc.contributor.author Arpí Llucià, Oriol
• dc.contributor.author Rovira Guerín, Ana
• dc.contributor.author Albanell Mestres, Joan
• dc.contributor.author Madoz-Gúrpide, Juan
• dc.contributor.author García-Foncillas, Jesús
• dc.contributor.author Rojo, Federico
• dc.date.accessioned 2023-02-02T13:30:09Z
• dc.date.available 2023-02-02T13:30:09Z
• dc.date.issued 2022
• dc.description.abstract Together with its reported ability to modulate AKT phosphorylation (p-AKT) status in several tumor types, the oncoprotein CIP2A has been described to induce breast cancer progression and drug resistance. However, the clinical and therapeutic relevance of the CIP2A/AKT interplay in breast cancer remains to be fully clarified. Here, we found high p-AKT levels in 80 out of 220 cases (36.4%), which were associated with negative estrogen receptor expression (p = 0.049) and CIP2A overexpression (p < 0.001). Interestingly, p-AKT determined substantially shorter overall (p = 0.002) and progression-free survival (p = 0.003), and multivariate analyses showed its CIP2A-independent prognostic value. Moreover, its clinical relevance was further confirmed in the triple negative and HER2-positive subgroups after stratifying our series by molecular subtype. Functionally, we confirmed in vitro the role of CIP2A as a regulator of p-AKT levels in breast cancer cell lines, and the importance of the CIP2A/AKT axis was also validated in vivo. Finally, p-AKT also showed a higher predictive value of response to doxorubicin than CIP2A in ex vivo analyses. In conclusion, our findings suggest that CIP2A overexpression is a key contributing event to AKT phosphorylation and highlights the CIP2A/AKT axis as a promising therapeutic target in breast cancer. However, our observations highlight the existence of alternative mechanisms that regulate AKT signaling in a subgroup of breast tumors without altered CIP2A expression that determines its independent value as a marker of poor outcome in this disease.
• dc.format.mimetype application/pdf
• dc.identifier.citation Luque M, Cristóbal I, Sanz-Álvarez M, Santos A, Zazo S, Eroles P, Arpí O, Rovira A, Albanell J, Madoz-Gúrpide J, García-Foncillas J, Rojo F. CIP2A as a key regulator for AKT phosphorylation has partial impact determining clinical outcome in breast cancer. J Clin Med. 2022 Mar 14;11(6):1610. DOI: 10.3390/jcm11061610
• dc.identifier.doi http://dx.doi.org/10.3390/jcm11061610
• dc.identifier.issn 2077-0383
• dc.identifier.uri http://hdl.handle.net/10230/55597
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof J Clin Med. 2022 Mar 14;11(6):1610
• dc.rights © 2022 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 (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword CIP2A
• dc.subject.keyword Early breast cancer
• dc.subject.keyword p-AKT
• dc.subject.keyword Prognosis
• dc.subject.keyword Therapy
• dc.title CIP2A as a key regulator for AKT phosphorylation has partial impact determining clinical outcome in breast cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion