Skip to main content
Top
Published in: Clinical and Translational Oncology 9/2017

01-09-2017 | Research Article

Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer

Authors: S. Hou, P. Du, P. Wang, C. Wang, P. Liu, H. Liu

Published in: Clinical and Translational Oncology | Issue 9/2017

Login to get access

Abstract

Background

Ovarian cancer is the most lethal gynecologic malignancy worldwide with surgery as the only curative treatment. Long-term overall survival (OS) of ovarian cancer is far from satisfactory, even though significant improvement has been made in post-operative chemotherapy. One of the most important death cause is the chemoresistance due to consecutive chemotherapy. Therefore, understanding the molecular mechanisms involved in ovarian cancer development and identification of novel therapeutic targets are urgently required.

Methods

Immunohistochemical (IHC) staining was used to explore the expression pattern of mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) in tumor tissues from 138 epithelial ovarian cancer (EOC) patients. Clinicopathological data were subjected to Kaplan–Meier survival and Cox multivariate analyses to evaluate the prognostic value of MNK1 in EOC. Overexpression and silencing procedures were performed on OVCAR-5 cells to investigate the mechanisms of MNK1 in regulating EOC development. The anti-tumor effects of CGP57380, a specific MNK inhibitor, were examined by cell viability assay.

Results

Higher MNK1 expression showed significant relationship with advanced FIGO stage and positive lymph node metastasis of EOC. Univariate and multivariate analyses revealed that MNK1 was an independent prognostic factor for OS of EOC patients. In vitro study demonstrated that MNK1 can promote cell proliferation through regulating the phosphorylation level of eukaryotic initiation factor 4E. In addition, inhibition of MNK1 by CGP57380 significantly down-regulated the OVCAR-5 cell viability.

Conclusion

High MNK1 expression in EOC tissues indicates poor clinical outcomes, and MNK1 can act as a potential target for novel chemotherapy development towards EOC.
Literature
2.
go back to reference Lalwani N, Prasad SR, Vikram R, Shanbhogue AK, Huettner PC, Fasih N. Histologic, molecular, and cytogenetic features of ovarian cancers: implications for diagnosis and treatment. Radiogr Rev Publ Radiol Soc N Am Inc. 2011;31(3):625–46. doi:10.1148/rg.313105066. Lalwani N, Prasad SR, Vikram R, Shanbhogue AK, Huettner PC, Fasih N. Histologic, molecular, and cytogenetic features of ovarian cancers: implications for diagnosis and treatment. Radiogr Rev Publ Radiol Soc N Am Inc. 2011;31(3):625–46. doi:10.​1148/​rg.​313105066.
4.
go back to reference Felix AS, Stone RA, Bowser R, Chivukula M, Edwards RP, Weissfeld JL, et al. Comparison of survival outcomes between patients with malignant mixed mullerian tumors and high-grade endometrioid, clear cell, and papillary serous endometrial cancers. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2011;21(5):877–84. doi:10.1097/IGC.0b013e31821a62dd.CrossRef Felix AS, Stone RA, Bowser R, Chivukula M, Edwards RP, Weissfeld JL, et al. Comparison of survival outcomes between patients with malignant mixed mullerian tumors and high-grade endometrioid, clear cell, and papillary serous endometrial cancers. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2011;21(5):877–84. doi:10.​1097/​IGC.​0b013e31821a62dd​.CrossRef
6.
go back to reference Buxade M, Parra-Palau JL, Proud CG. The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front Biosci J Virtual Libr. 2008;13:5359–73.CrossRef Buxade M, Parra-Palau JL, Proud CG. The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Front Biosci J Virtual Libr. 2008;13:5359–73.CrossRef
11.
go back to reference Bell JB, Eckerdt F, Alley K, Magnusson LP, Hussain H, Bi Y, et al. MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma. Mol Cancer Res MCR. 2016. doi:10.1158/1541-7786.mcr-16-0172. Bell JB, Eckerdt F, Alley K, Magnusson LP, Hussain H, Bi Y, et al. MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma. Mol Cancer Res MCR. 2016. doi:10.​1158/​1541-7786.​mcr-16-0172.
16.
20.
go back to reference Jones RM, MacDonald ME, Branda J, Altherr MR, Louis DN, Schmidt EV. Assignment of the human gene encoding eukaryotic initiation factor 4E (EIF4E) to the region q21-25 on chromosome 4. Somat Cell Mol Genet. 1997;23(3):221–3.CrossRefPubMed Jones RM, MacDonald ME, Branda J, Altherr MR, Louis DN, Schmidt EV. Assignment of the human gene encoding eukaryotic initiation factor 4E (EIF4E) to the region q21-25 on chromosome 4. Somat Cell Mol Genet. 1997;23(3):221–3.CrossRefPubMed
24.
25.
go back to reference Wolf JK, Jenkins AD. Gene therapy for ovarian cancer (review). Int J Oncol. 2002;21(3):461–8.PubMed Wolf JK, Jenkins AD. Gene therapy for ovarian cancer (review). Int J Oncol. 2002;21(3):461–8.PubMed
26.
go back to reference Noske A, Lindenberg JL, Darb-Esfahani S, Weichert W, Buckendahl AC, Roske A, et al. Activation of mTOR in a subgroup of ovarian carcinomas: correlation with p-eIF-4E and prognosis. Oncol Rep. 2008;20(6):1409–17.PubMed Noske A, Lindenberg JL, Darb-Esfahani S, Weichert W, Buckendahl AC, Roske A, et al. Activation of mTOR in a subgroup of ovarian carcinomas: correlation with p-eIF-4E and prognosis. Oncol Rep. 2008;20(6):1409–17.PubMed
28.
go back to reference Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382–92. doi:10.1056/NEJMoa1105535.CrossRefPubMed Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382–92. doi:10.​1056/​NEJMoa1105535.CrossRefPubMed
Metadata
Title
Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer
Authors
S. Hou
P. Du
P. Wang
C. Wang
P. Liu
H. Liu
Publication date
01-09-2017
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 9/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-017-1646-x

Other articles of this Issue 9/2017

Clinical and Translational Oncology 9/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine