ArticleThe Journal of clinical investigation2014
Menin determines K-RAS proliferative outputs in endocrine cells.
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 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 70 citations in OpenAlex.
- RSPO1, a potent inducer of pancreatic β cell neogenesis.Cell reports. Medicine · 2025Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Type 2 diabetes susceptibility gene GRK5 regulates physiological pancreatic β-cell proliferation via phosphorylation of HDAC5.iScience · 2023Article
- The role of DNA methylation in human pancreatic neuroendocrine tumours.Endocrine oncology (Bristol, England) · 2023Review
- The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α.Nature communications · 2022Article
- Modeling MEN1 with Patient-Origin iPSCs Reveals GLP-1R Mediated Hypersecretion of Insulin.Cells · 2022Article
- Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells.The Journal of clinical investigation · 2022Article
- Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment.Biomedicines · 2022Review
- Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers.International journal of molecular sciences · 2022Review
- Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors.Frontiers in oncology · 2022Review
- Article
- New Aspects of Diabetes Research and Therapeutic Development.Pharmacological reviews · 2021Review
- Multiple Endocrine Neoplasia Type 1: Latest Insights.Endocrine reviews · 2021Review
- Mitogen Synergy: An Emerging Route to Boosting Human Beta Cell Proliferation.Frontiers in cell and developmental biology · 2021Review
- Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.Frontiers in endocrinology · 2021Review
- The Hippo Tumor Suppressor Pathway (YAP/TAZ/TEAD/MST/LATS) and EGFR-RAS-RAF-MEK in cancer metastasis.Genes & diseases · 2021Review
- The RASSF1A Tumor Suppressor Binds the RasGAP DAB2IP and Modulates RAS Activation in Lung Cancer.Cancers · 2020Article
- Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (Journal of the Endocrine Society · 2020Article
- Generation and characterization of CRISPR/Cas9-mediated MEN1 knockout BON1 cells: a human pancreatic neuroendocrine cell line.Scientific reports · 2020Article
- Genetic background influences tumour development in heterozygous Men1 knockout mice.Endocrine connections · 2020Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
Abstract
Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K-RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS-activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself, but synergistically enhanced proliferation when combined with a menin inhibitor. In contrast, inhibition of MAPK signaling created a synthetic lethal interaction in the setting of menin loss. These insights suggest potential strategies both for regenerating pancreatic β cells for people with diabetes and for targeting menin-sensitive endocrine tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.