ArticleMolecular cancer research : MCR2016
Differential Regulation of ZEB1 and EMT by MAPK-Interacting Protein Kinases (MNK) and eIF4E in Pancreatic Cancer.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 66 citations in OpenAlex.
- ZEB1 and Uveal Melanoma Invasiveness.International journal of molecular sciences · 2025Article
- MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation.Journal of experimental & clinical cancer research : CR · 2024Article
- Interactions between circRNAs and miR-141 in Cancer: From Pathogenesis to Diagnosis and Therapy.International journal of molecular sciences · 2023Review
- Article
- Pancreatic Cancer Organoids: An Emerging Platform for Precision Medicine?Biomedicines · 2023Review
- An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer.Molecular therapy. Nucleic acids · 2022Article
- Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis.Cancers · 2022Review
- Knockdown of hnRNPA1 Promotes NSCLC Metastasis and EMT by Regulating Alternative Splicing of LAS1L exon 9.Frontiers in oncology · 2022Article
- Review
- Inhibiting the MNK1/2-eIF4E axis impairs melanoma phenotype switching and potentiates antitumor immune responses.The Journal of clinical investigation · 2021Article
- Phosphorylation of the mRNA cap-binding protein eIF4E and cancer.Cellular signalling · 2020Review
- Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer.International journal of molecular sciences · 2020Review
- WD Repeat Domain 5 Promotes Invasion, Metastasis and Tumor Growth in Glioma Through Up-Regulated Zinc Finger E-Box Binding Homeobox 1 Expression.Cancer management and research · 2020Article
- Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway.International journal of molecular medicine · 2020Article
- Review
- Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma.Oncotarget · 2019Article
- Pancreatic Progenitors and Organoids as a Prerequisite to Model Pancreatic Diseases and Cancer.Stem cells international · 2019Review
- Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD-L1 in pancreatic stellate cells.Scientific reports · 2018Article
- eIF4E Phosphorylation in Prostate Cancer.Neoplasia (New York, N.Y.) · 2018Review
- Translation initiation factors and their relevance in cancer.Current opinion in genetics & development · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledHuman pancreatic ductal adenocarcinoma (PDAC) tumors are associated with dysregulation of mRNA translation. In this report, it is demonstrated that PDAC cells grown in collagen exhibit increased activation of the MAPK-interacting protein kinases (MNK) that mediate eIF4E phosphorylation. Pharmacologic and genetic targeting of MNKs reverse epithelial-mesenchymal transition (EMT), decrease cell migration, and reduce protein expression of the EMT-regulator ZEB1 without affecting ZEB1 mRNA levels. Paradoxically, targeting eIF4E, the best-characterized effector of MNKs, increases ZEB1 mRNA expression through repression of ZEB1-targeting miRNAs, miR-200c and miR-141. In contrast, targeting the MNK effector hnRNPA1, which can function as a translational repressor, increases ZEB1 protein without increasing ZEB1 mRNA levels. Importantly, treatment with MNK inhibitors blocks growth of chemoresistant PDAC cells in collagen and decreases the number of aldehyde dehydrogenase activity-positive (Aldefluor+) cells. Significantly, MNK inhibitors increase E-cadherin mRNA levels and decrease vimentin mRNA levels in human PDAC organoids without affecting ZEB1 mRNA levels. Importantly, MNK inhibitors also decrease growth of human PDAC organoids. IMPLICATIONS: These results demonstrate differential regulation of ZEB1 and EMT by MNKs and eIF4E, and identify MNKs as potential targets in pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.