Research Papers:

Inhibiting the MNK-eIF4E-β-catenin axis increases the responsiveness of aggressive breast cancer cells to chemotherapy

Zhiqiang Li, Yang Sun, Miao Qu, Hongxing Wan, Fang Cai and Peng Zhang _

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Oncotarget. 2017; 8:2906-2915. https://doi.org/10.18632/oncotarget.13772

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Zhiqiang Li1, Yang Sun1, Miao Qu2, Hongxing Wan1, Fang Cai3, Peng Zhang4

1Department of Oncology, Sanya People’s Hospital, Sanya 572000, China

2Special Care Unit, Sanya People’s Hospital, Sanya 572000, China

3Department of Pharmacy, Sanya People’s Hospital, Sanya 572000, China

4Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Correspondence to:

Peng Zhang, email: [email protected]

Keywords: breast cancer, chemoresistance, MNK, eIF4E, β-catenin

Received: September 09, 2016     Accepted: November 22, 2016     Published: December 01, 2016


Advanced breast cancer (eg. stage IV) is resistant to chemotherapy. In this work, we identified potentially druggable targets that are critically involved in chemoresistance. We showed that eIF4E is highly phosphorylated at serine 209 in breast cancer patients in response to chemotherapy, which significantly correlated with poorer clinical responses and outcomes. Depletion of eIF4E enhanced the anti-proliferative and pro-apoptotic effects of chemotherapeutic drugs in breast cancer cells. Chemotherapy activated the Wnt/β-catenin signaling in an eIF4E-dependent manner. However, MNK inhibitors prevented chemotherapeutic drug-induced eIF4E phosphorylation and β-catenin activation, which enhanced the breast cancer cell response to chemotherapy in vitro and in vivo. These findings indicate MNK-eIF4E-β-catenin is an activator of the breast cancer cell response to chemotherapy and highlights the therapeutic value of inhibiting MNK to overcome chemoresistance in breast cancer.

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