ArticleThe Journal of clinical investigation2014
IER3 supports KRASG12D-dependent pancreatic cancer development by sustaining ERK1/2 phosphorylation.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 48 citations in OpenAlex.
- Post-Translational Modifications in Pancreatic Cancer: Mechanisms to Clinical Applications.Journal of gastroenterology and hepatology · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- Unveiling the developmental and tumor-suppressive roles of the p53 variant p53psi.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- IER3 Promotes Malignant Progression of Colorectal Cancer Through the NF-International journal of genomics · 2026Article
- Single-Cell Dissection of the Serrated Pathway: Cellular Heterogeneity and Genetic Causality in Colorectal Cancer.International journal of molecular sciences · 2025Article
- PLCH1 overexpression promotes breast cancer progression and predicts poor prognosis through the ERK1/2-EGR1 axis.Frontiers in oncology · 2025Article
- Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.International journal of biological sciences · 2025Review
- The biological and immunological significance of the estrogen-related gene IER3 in diabetes.Frontiers in endocrinology · 2025Article
- Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice.The American journal of pathology · 2024Article
- Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma.Cancer cell international · 2024Article
- Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.World journal of otorhinolaryngology - head and neck surgery · 2024Article
- Exploring Hypertrophic Cardiomyopathy Biomarkers through Integrated Bioinformatics Analysis: Uncovering Novel Diagnostic Candidates.Cardiology research and practice · 2024Article
- Single-Nucleus Transcriptome Profiling of Locally Advanced Cervical Squamous Cell Cancer Identifies Neural-Like Progenitor Program Associated with the Efficacy of Radiotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Review
- Molecular signaling in pancreatic ductal metaplasia: emerging biomarkers for detection and intervention of early pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Article
- Integrated single-cell and bulk RNA sequencing analyses reveal a prognostic signature of cancer-associated fibroblasts in head and neck squamous cell carcinoma.Frontiers in genetics · 2022Article
- S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways.Cell biology and toxicology · 2021Article
- Models that combine transcriptomic with spatial protein information exceed the predictive value for either single modality.NPJ precision oncology · 2021Article
- Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A.Oncology letters · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Activating mutations in the KRAS oncogene are prevalent in pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that pancreatic intraepithelial neoplasia (PanIN) formation, which precedes malignant transformation, associates with the expression of immediate early response 3 (Ier3) as part of a prooncogenic transcriptional pathway. Here, we evaluated the role of IER3 in PanIN formation and PDAC development. In human pancreatic cancer cells, IER3 expression efficiently sustained ERK1/2 phosphorylation by inhibiting phosphatase PP2A activity. Moreover, IER3 enhanced KrasG12D-dependent oncogenesis in the pancreas, as both PanIN and PDAC development were delayed in IER3-deficient KrasG12D mice. IER3 expression was discrete in healthy acinar cells, becoming highly prominent in peritumoral acini, and particularly high in acinar ductal metaplasia (ADM) and PanIN lesions, where IER3 colocalized with phosphorylated ERK1/2. However, IER3 was absent in undifferentiated PDAC, which suggests that the IER3-dependent pathway is an early event in pancreatic tumorigenesis. IER3 expression was induced by both mild and severe pancreatitis, which promoted PanIN formation and progression to PDAC in KrasG12D mice. In IER3-deficient mice, pancreatitis abolished KrasG12D-induced proliferation, which suggests that pancreatitis enhances the oncogenic effect of KRAS through induction of IER3 expression. Together, our data indicate that IER3 supports KRASG12D-associated oncogenesis in the pancreas by sustaining ERK1/2 phosphorylation via phosphatase PP2A inhibition.
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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.