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• W2950873557 abstract "Targeting β-catenin has been shown to have great potential therapeutic value in cervical cancer. Because β-catenin is also essential for normal cells, strategies to specifically target cancer will require identification of druggable factors capable of distinguishing β-catenin signaling pathways between cancer and normal cells.Expression of p-eIF4E and p-β-catenin was analyzed in malignant and normal cervical tissues and cells. The effects and its underlying mechanisms of targeting MNK and eukaryotic translation initiation factor 4E (eIF4E) were determined in cervical cancer and normal cells.Inhibiting MNK/eIF4E axis selectively targets cervical cancer without affecting normal cervical cells, via suppressing eIF4E-mediated β-catenin activation. We found that eIF4E phosphorylation was upregulated in cervical cancer cells and tissues but not normal cervical counterparts, and its phosphorylation at Ser 209 activates Wnt/β-catenin signaling, promotes growth and migration in cervical cancer, in an MNK-dependent manner. MNK inhibition via genetic small interfering RNA (siRNA) knockdown or pharmacologic inhibitor effectively decreased phosphorylation of eIF4E and β-catenin, leading to reduced β-catenin activity and transcript levels of Wnt target genes in cervical cancer cells. Consistently, we found that MNK kinase inhibitor is effective in inhibiting proliferation and migration, and inducing apoptosis in cervical cancer but not normal cervical cells. The combination of MNK kinase inhibitor with paclitaxel achieved greater efficacy in cervical cancer cells than paclitaxel alone.Our work identifies MNK-eIF4E axis as a specific and critical regulator of β-catenin activity in cervical cancer but not normal cervical cells, and suggests that targeting MNK is a useful therapeutic strategy in cervical cancer." @default.
• W2950873557 created "2019-06-27" @default.
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• W2950873557 date "2019-09-01" @default.
• W2950873557 modified "2023-09-25" @default.
• W2950873557 title "Inhibiting MNK Selectively Targets Cervical Cancer via Suppressing eIF4E-Mediated β-Catenin Activation" @default.
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• W2950873557 doi "https://doi.org/10.1016/j.amjms.2019.05.013" @default.
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