Portal de investigación
CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer.
Fecha de publicación:
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Autores de INCLIVA
Participantes ajenos a INCLIVA
- Luque, M
- Cristobal, I
- Sanz-Alvarez, M
- Santos, A
- Zazo, S
- Arpi, O
- Rovira, A
- Albanell, J
- Madoz-Gurpide, J
- Garcia-Foncillas, J
- Rojo, F
Grupos y Plataformas de I+D+i
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.
Datos de la publicación
- ISSN/ISSNe:
- 2077-0383, 2077-0383
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.3390/jcm11061610
- PubMed:
- 35329936
Journal of Clinical Medicine MDPI
Citas Recibidas en Web of Science: 3
Documentos
Filiaciones
Keywords
- CIP2A; early breast cancer; p-AKT; prognosis; therapy
Financiación
Proyectos y Estudios Clínicos
Caracterizacion y repercusion terapeutica de la ecologia de cancer de mama HER2 positivo
Investigador Principal: PILAR EROLES ASENSIO
PI18/01219 . INSTITUTO SALUD CARLOS III . 2019
Cita
Luque M,Cristobal I,Sanz M,Santos A,Zazo S,Eroles P,Arpi O,Rovira A,Albanell J,Madoz J,Garcia J,Rojo F. CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer. J. Clin. Med. 2022. 11. (6):1610. IF:3,900. (2).
CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer. Luque M, Cristobal I, Sanz M, Santos A, Zazo S, Eroles P, Arpi O et al. Journal of Clinical Medicine. 2022 marzo 14. 11 (6):DOI:10.3390/jcm11061610. PMID:35329936.
