ArticlePloS one2013
The MEK/ERK pathway promotes NOTCH signalling in pancreatic cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- High IntratumoralInternational journal of molecular sciences · 2026Pooled it
- Notch Signaling in Spinal Cord Injury: Mechanistic Insights and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- Notch Signaling Is Associated with LED Light-Regulated Papilla Regeneration in the Sea Cucumber (International journal of molecular sciences · 2026Article
- Hesperetin induces apoptosis in lung squamous carcinoma cells via GInternational journal of molecular medicine · 2025Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Article
- Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors.Nature communications · 2024Article
- Article
- A stop-gain mutation in GXYLT1 promotes metastasis of colorectal cancer via the MAPK pathway.Cell death & disease · 2022Article
- An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.Frontiers in oncology · 2022Review
- Article
- Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein.Molecular neurobiology · 2021Article
- Targeted Therapies for Pancreatic Cancer.Cancers · 2018Review
- Article
- C-terminal deletion of NOTCH1 intracellular domain (N1Scientific reports · 2017Article
- Role of Notch signaling pathway in pancreatic cancer.American journal of cancer research · 2017Review
- MMP-9 signaling in the left ventricle following myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2016Review
- MEK1 signaling promotes self-renewal and tumorigenicity of liver cancer stem cells via maintaining SIRT1 protein stabilization.Oncotarget · 2016Article
- Inhibition of perillyl alcohol on cell invasion and migration depends on the Notch signaling pathway in hepatoma cells.Molecular and cellular biochemistry · 2016Article
- Regulating Axonal Responses to Injury: The Intersection between Signaling Pathways Involved in Axon Myelination and The Inhibition of Axon Regeneration.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Activation of the NOTCH receptors relies on their intracellular proteolysis by the gamma-secretase complex. This cleavage liberates the NOTCH intracellular domain (NIC) thereby allowing the translocation of NIC towards the nucleus to assemble into a transcriptional platform. Little information is available regarding the regulatory steps operating on NIC following its release from the transmembrane receptor up to its association with transcriptional partners. Interfering with these regulatory steps might potentially influences the nuclear outcome of NOTCH signalling. Herein, we exploited a reliable model to study the molecular events occurring subsequent to NOTCH1 cleavage. In pancreatic cancer cells, pulse of NOTCH1 activation led to increased expression of NOTCH target genes namely HES1 and c-MYC. We uncovered that, upon its release, the NOTCH1 intracellular domain, NIC1, undergoes a series of post-translational modifications that include phosphorylation. Most interestingly, we found that activation of the MEK/ERK pathway promotes HES1 expression. Inhibition of the gamma-secretase complex prevented the MEK/ERK-induced HES1 expression suggesting a NOTCH-dependent mechanism. Finally, higher levels of NIC1 were found associated with its transcriptional partners [CBF1, Su(H) and LAG-1] (CSL) and MASTERMIND-LIKE 1 (MAML1) upon MEK/ERK activation providing a potential mechanism whereby the MEK/ERK pathway promotes expression of NOTCH target genes. For the first time, our data exposed a signalling pathway, namely the MEK/ERK pathway that positively impacts on NOTCH nuclear outcome.
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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.