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/beta-catenin signaling in an eIF4E-dependent manner. However, MNK inhibitors prevented chemotherapeutic drug-induced eIF4E phosphorylation and beta-catenin activation, which enhanced the breast cancer cell response to chemotherapy in vitro and in vivo. These findings indicate MNK-eIF4E-beta-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.
基金：
National Nature Science Foundation of China [81202095]
第一作者单位：[1]Sanya Peoples Hosp, Dept Oncol, Sanya 572000, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Li Zhiqiang,Sun Yang,Qu Miao,et al.Inhibiting the MNK-eIF4E-β-catenin axis increases the responsiveness of aggressive breast cancer cells to chemotherapy[J].ONCOTARGET.2017,8(2):2906-2915.doi:10.18632/oncotarget.13772.
APA：
Li, Zhiqiang,Sun, Yang,Qu, Miao,Wan, Hongxing,Cai, Fang&Zhang, Peng.(2017).Inhibiting the MNK-eIF4E-β-catenin axis increases the responsiveness of aggressive breast cancer cells to chemotherapy.ONCOTARGET,8,(2)
MLA：
Li, Zhiqiang,et al."Inhibiting the MNK-eIF4E-β-catenin axis increases the responsiveness of aggressive breast cancer cells to chemotherapy".ONCOTARGET 8..2(2017):2906-2915
医学