ArticlePancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
The HMGA1-COX-2 axis: a key molecular pathway and potential target in pancreatic adenocarcinoma.
Article in Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 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
- HMGA1 is associated with unfavorable outcome and accelerates the aggressiveness of cholangiocarcinoma.SAGE open medicine · 2026Article
- High Mobility Group A1 Chromatin Keys: Unlocking the Genome During MPN Progression.International journal of molecular sciences · 2025Review
- HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis.The Journal of clinical investigation · 2025Article
- HMGA1 induces FGF19 to drive pancreatic carcinogenesis and stroma formation.The Journal of clinical investigation · 2023Article
- Blockade of the protease ADAM17 ameliorates experimental pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential.International journal of biological sciences · 2022Review
- Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma.Cell death discovery · 2021Article
- Mesenchymal stromal cells expressing a dominant-negative high mobility group A1 transgene exhibit improved function during sepsis.Journal of leukocyte biology · 2021Article
- HMGA1, Moonlighting Protein Function, and Cellular Real Estate: Location, Location, Location!Biomolecules · 2021Review
- High mobility group A1 (HMGA1) protein and gene expression correlate with ER-negativity and poor outcomes in breast cancer.Breast cancer research and treatment · 2020Article
- Celecoxib combined with salirasib strongly inhibits pancreatic cancer cells in 2D and 3D cultures.International journal of medical sciences · 2020Article
- Clinical Implications of Extracellular HMGA1 in Breast Cancer.International journal of molecular sciences · 2019Review
- Immunomodulatory Nanosystems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Review
- HMGA1 in cancer: Cancer classification by location.Journal of cellular and molecular medicine · 2019Review
- Mandatory role of HMGA1 in human airway epithelial normal differentiation and post-injury regeneration.Oncotarget · 2018Article
- Lipopolysaccharide Stimulated the Migration of NIH3T3 Cells Through a Positive Feedback Between β-Catenin and COX-2.Frontiers in pharmacology · 2018Article
- IL-24 modulates the high mobility group (HMG) A1/miR222 /AKT signaling in lung cancer cells.Oncotarget · 2016Article
- The High Mobility Group A1 (HMGA1) gene is highly overexpressed in human uterine serous carcinomas and carcinosarcomas and drives Matrix Metalloproteinase-2 (MMP-2) in a subset of tumors.Gynecologic oncology · 2016Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
contextAlthough pancreatic cancer is a common, highly lethal malignancy, the molecular events that enable precursor lesions to become invasive carcinoma remain unclear. We previously reported that the high-mobility group A1 (HMGA1) protein is overexpressed in >90% of primary pancreatic cancers, with absent or low levels in early precursor lesions.
methodsHere, we investigate the role of HMGA1 in reprogramming pancreatic epithelium into invasive cancer cells. We assessed oncogenic properties induced by HMGA1 in non-transformed pancreatic epithelial cells expressing activated K-RAS. We also explored the HMGA1-cyclooxygenase (COX-2) pathway in human pancreatic cancer cells and the therapeutic effects of COX-2 inhibitors in xenograft tumorigenesis.
resultsHMGA1 cooperates with activated K-RAS to induce migration, invasion, and anchorage-independent cell growth in a cell line derived from normal human pancreatic epithelium. Moreover, HMGA1 and COX-2 expression are positively correlated in pancreatic cancer cell lines (r(2) = 0.93; p < 0.001). HMGA1 binds directly to the COX-2 promoter at an AT-rich region in vivo in three pancreatic cancer cell lines. In addition, HMGA1 induces COX-2 expression in pancreatic epithelial cells, while knock-down of HMGA1 results in repression of COX-2 in pancreatic cancer cells. Strikingly, we also discovered that Sulindac (a COX-1/COX-2 inhibitor) or Celecoxib (a more specific COX-2 inhibitor) block xenograft tumorigenesis from pancreatic cancer cells expressing high levels of HMGA1.
conclusionsOur studies identify for the first time an important role for the HMGA1-COX-2 pathway in pancreatic cancer and suggest that targeting this pathway could be effective to treat, or even prevent, pancreatic cancer.
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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.