Oncotarget

Research Papers:

Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer

Celia Pinto-Díez, Eva M. García-Recio, M. Isabel Pérez-Morgado, Marta García-Hernández, Lara Sanz-Criado, Silvia Sacristán, M. Val Toledo-Lobo, Belén Pérez-Mies, Isabel Esteban-Rodríguez, Alejandro Pascual, Mercedes Garcia-Villanueva, Noelia Martínez-Jañez, Víctor M. González and M. Elena Martín _

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Oncotarget. 2018; 9:13501-13516. https://doi.org/10.18632/oncotarget.24417

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Abstract

Celia Pinto-Díez1,*, Eva M. García-Recio1,*, M. Isabel Pérez-Morgado1, Marta García-Hernández1, Lara Sanz-Criado1, Silvia Sacristán1, M. Val Toledo-Lobo2, Belén Pérez-Mies3, Isabel Esteban-Rodríguez4, Alejandro Pascual3, Mercedes Garcia-Villanueva3, Noelia Martínez-Jañez5, Víctor M. González1 and M. Elena Martín1

1Servicio de Bioquímica-Investigación, IRYCIS-Hospital Ramón y Cajal, Madrid, Spain

2Departamento de Biomedicina y Biotecnología, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

3Servicio de Anatomía Patológica, IRYCIS-Hospital Ramón y Cajal, Madrid, Spain

4Sevicio de Anatomía Patológica, IDYPAZ-Hospital La Paz, Madrid, Spain

5Servicio de Oncología, IRYCIS-Hospital Ramón y Cajal, Madrid, Spain

*These authors contributed equally to this work

Correspondence to:

M. Elena Martín, email: m.elena.martin@hrc.es

Víctor M. González, email: victor.m.gonzalez@hrc.es

Keywords: breast cancer; MNK1; molecular tumor type; pronostic marker; triple-negative

Received: May 18, 2017     Accepted: January 31, 2018     Published: February 05, 2018

ABSTRACT

MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer. MNK1a and MNK1b expression was significantly increased in tumors relative to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b overexpression was found in most of the triple-negative tumors and was associated with a shorter overall and disease-free survival time. Overexpression of MNK1b in MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic protein and promoted proliferation, invasion and colony formation. In conclusion, a high expression level of MNK1b protein could be used as a marker of poor prognosis in breast cancer patients and it could be a therapeutic target in triple-negative tumors.


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