ArticleMolecular cancer therapeutics2012
Cell intrinsic role of COX-2 in pancreatic cancer development.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Cancer-associated fibroblast subtypes differentially modulate natural killer cells in cancer.Cell reports · 2026Article
- Ecto-5'-nucleotidase/CD73 reduces COX-2 expression in activated macrophages.Scientific reports · 2026Article
- Cyclooxygenases in pancreatic ductal adenocarcinoma: are they inflammatory catalysts for tumor growth.Frontiers in oncology · 2026Review
- Mechanistic and functional characterization of ABTB2 as a novel target for pancreatic cancer therapy.Molecular therapy. Oncology · 2025Article
- P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.Purinergic signalling · 2025Article
- Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.Molecular and cellular biochemistry · 2025Review
- Chronic pancreatitis as a driving factor for pancreatic cancer: An epidemiological understanding.World journal of clinical oncology · 2024Article
- High hypoxia status in pancreatic cancer is associated with multiple hallmarks of an immunosuppressive tumor microenvironment.Frontiers in immunology · 2024Article
- Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer.Pharmaceutics · 2023Article
- The Expressions of NF-κB, COX-2, Sp1, and c-Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Article
- The EPH/Ephrin System in Pancreatic Ductal Adenocarcinoma (PDAC): From Pathogenesis to Treatment.International journal of molecular sciences · 2023Review
- Study of the antioxidant and anti-pancreatic cancer activities ofFrontiers in pharmacology · 2023Article
- DNA Polymerase Theta Plays a Critical Role in Pancreatic Cancer Development and Metastasis.Cancers · 2022Article
- Matrix stiffness mediates pancreatic cancer chemoresistance through induction of exosome hypersecretion in a cancer associated fibroblasts-tumor organoid biomimetic model.Matrix biology plus · 2022Article
- Prognostic role of IRS-4 in the survival of patients with pancreatic cancer.Histology and histopathology · 2022Article
- RAS-mediated tumor stress adaptation and the targeting opportunities it presents.Disease models & mechanisms · 2022Article
- Coordinated regulation of immune contexture: crosstalk between STAT3 and immune cells during breast cancer progression.Cell communication and signaling : CCS · 2021Review
- A naturally derived small molecule PSM0537 targets the AF1Q-TCF4 interaction to suppress COX2 expression and inhibit cell proliferation and metastasis in osteosarcoma.American journal of cancer research · 2021Article
- The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
COX-2 is upregulated in pancreatic ductal adenocarcinomas (PDAC). However, how COX-2 promotes PDAC development is unclear. While previous studies have evaluated the efficacy of COX-2 inhibition via the use of nonsteroidal anti-inflammatory drugs (NSAID) or the COX-2 inhibitor celecoxib in PDAC models, none have addressed the cell intrinsic versus microenvironment roles of COX-2 in modulating PDAC initiation and progression. We tested the cell intrinsic role of COX-2 in PDAC progression using both loss-of-function and gain-of-function approaches. Cox-2 deletion in Pdx1+ pancreatic progenitor cells significantly delays the development of PDAC in mice with K-ras activation and Pten haploinsufficiency. Conversely, COX-2 overexpression promotes early onset and progression of PDAC in the K-ras mouse model. Loss of PTEN function is a critical factor in determining lethal PDAC onset and overall survival. Mechanistically, COX-2 overexpression increases p-AKT levels in the precursor lesions of Pdx1(+); K-ras(G12D)(/+); Pten(lox)(/+) mice in the absence of Pten LOH. In contrast, Cox-2 deletion in the same setting diminishes p-AKT levels and delays cancer progression. These data suggest an important cell intrinsic role for COX-2 in tumor initiation and progression through activation of the PI3K/AKT pathway. PDAC that is independent of intrinsic COX-2 expression eventually develops with decreased FKBP5 and increased GRP78 expression, two alternate pathways leading to AKT activation. Together, these results support a cell intrinsic role for COX-2 in PDAC development and suggest that while anti-COX-2 therapy may delay the development and progression of PDAC, mechanisms known to increase chemoresistance through AKT activation must also be overcome.
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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.