ArticleGastroenterology2014
MAPK signaling is required for dedifferentiation of acinar cells and development of pancreatic intraepithelial neoplasia in mice.
Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 132 citations in OpenAlex.
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Metabolic Syndrome and Pancreatic Cancer: Linking Insulin Resistance, Inflammation, and Carcinogenesis.Diagnostics (Basel, Switzerland) · 2026Review
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Quantitative 3D histology reveals localized immune remodeling during early pancreatic cancer progression.Cell press blue · 2026Article
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Acinar-specific loss of activating transcription factor 3 restricts KRASCell death discovery · 2025Article
- Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data.Scientific reports · 2025Article
- Elucidation of roles of serine/threonine phosphatases PP1 and PP2A in mediating CCK-stimulated growth and enzyme secretion in pancreatic acinar cells.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition.Cancer research · 2025Article
- The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.Gastroenterology · 2024Review
- Inactivation of HIPK2 attenuates KRASJournal of experimental & clinical cancer research : CR · 2024Article
- 3D histology reveals that immune response to pancreatic precancers is heterogeneous and depends on global pancreas structure.bioRxiv : the preprint server for biology · 2024Article
- Inhibitory Effect of TCF7L2 on Pancreatic β-Cell Dedifferentiation via ERK/MAPK Signaling Pathway in Diabetes.Clinical medicine insights. Endocrinology and diabetes · 2024Article
- Cellular collusion: cracking the code of immunosuppression and chemo resistance in PDAC.Frontiers in immunology · 2024Review
- Oncogenic KRAS, Mucin 4, and Activin A-Mediated Fibroblast Activation Cooperate for PanIN Initiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Glucose-6-phosphate dehydrogenase deficiency accelerates pancreatic acinar-to-ductal metaplasia.bioRxiv : the preprint server for biology · 2023Article
- Targeting ribosome biogenesis reinforces ERK-dependent senescence in pancreatic cancer.Cell cycle (Georgetown, Tex.) · 2023Article
- Pancreatic acinar cell fate relies on system xCell death & disease · 2023Article
- Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer.Cancer discovery · 2023Article
- Acinar-to-Ductal Metaplasia (ADM): On the Road to Pancreatic Intraepithelial Neoplasia (PanIN) and Pancreatic Cancer.International journal of molecular sciences · 2023Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsKras signaling via mitogen-activated protein kinase (MAPK) is highly up-regulated in pancreatic cancer cells. We investigated whether MAPK signaling is required for the initiation and maintenance of pancreatic carcinogenesis in mice.
methodsWe studied the formation and maintenance of pancreatic intraepithelial neoplasia (PanINs) in p48Cre; TetO-KrasG12D; Rosa26(rtTa-IRES-EGFP) (iKras*) mice and LSL-KrasG12D mice bred with p48Cre mice (KC). Mice were given oral PD325901, a small-molecule inhibitor of MEK1 and MEK2 (factors in the MAPK signaling pathway), along with injections of cerulein to induce pancreatitis. Other mice were given PD325901 only after PanINs developed. Pancreatic tissues were collected and evaluated using histologic, immunohistochemical, immunofluorescence, and electron microscopy analyses. Acinar cells were isolated from the tissues and the effects of MEK1 and 2 inhibitors were assessed.
resultsPD325901 prevented PanIN formation, but not pancreatitis, in iKras* and KC mice. In iKras* or KC mice given PD325901 at 5 weeks after PanINs developed, PanINs regressed and acinar tissue regenerated. The regression occurred through differentiation of the PanIN cells to acini, accompanied by re-expression of the acinar transcription factor Mist1.
conclusionsIn iKras* and KC mice, MAPK signaling is required for the initiation and maintenance of pancreatic cancer precursor lesions. MAPK signaling promotes formation of PanINs by enabling dedifferentiation of acinar cells into duct-like cells that are susceptible to transformation.
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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.