Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer
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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
M. Elena Martín, email: [email protected]
Víctor M. González, email: [email protected]
Keywords: breast cancer; MNK1; molecular tumor type; pronostic marker; triple-negative
Received: May 18, 2017 Accepted: January 31, 2018 Published: February 05, 2018
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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