ArticlePloS one2013
Three-dimensional collagen I promotes gemcitabine resistance in vitro in pancreatic cancer cells through HMGA2-dependent histone acetyltransferase expression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- Comprehensive characterization of extracellular matrix-related genes in PAAD identified a novel prognostic panel related to clinical outcomes and immune microenvironment: A silico analysis withFrontiers in immunology · 2022Trial
- Lactate-induced epithelial-mesenchymal transition: a metabolic nexus in pancreatic cancer metastasis.Translational cancer research · 2026Review
- Advances in pancreatic cancer epigenetics: From the mechanism to the clinic.World journal of gastrointestinal oncology · 2025Review
- The type I collagen paradox in PDAC progression: microenvironmental protector turned tumor accomplice.Journal of translational medicine · 2025Review
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer.Biomedicines · 2024Review
- The Noncanonical Functions of Metabolites in Tumor Progression.Metabolites · 2024Review
- HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells.Cell death & disease · 2024Article
- A stumbling block in pancreatic cancer treatment: drug resistance signaling networks.Frontiers in cell and developmental biology · 2024Review
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.Bioengineering (Basel, Switzerland) · 2023Article
- Beyond matrix stiffness: targeting force-induced cancer drug resistance.Trends in cancer · 2023Review
- Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling.International journal of molecular sciences · 2023Article
- Thymoquinone affects the gemcitabine sensitivity of pancreatic cancer by regulating collagen via hypoxia inducible factor-1α.Frontiers in pharmacology · 2023Article
- Three-dimensional in vitro culture models in oncology research.Cell & bioscience · 2022Review
- lncRNA HIT000218960 enhances resistance to 5-fluorouracil by promoting HMGA2 and activating the AKT/mTOR/P70S6K pathway in gastric cancer cells.Experimental and therapeutic medicine · 2022Article
- Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers.Cancers · 2022Review
- A new era: tumor microenvironment in chemoresistance of pancreatic cancer.Journal of cancer science and clinical therapeutics · 2022Article
- MicroRNA-9-5p increases the sensitivity of colorectal cancer cells to 5-fluorouracil by downregulating high mobility group A2 expression.Oncology letters · 2021Article
- Stellate Cells Aid Growth-Permissive Metabolic Reprogramming and Promote Gemcitabine Chemoresistance in Pancreatic Cancer.Cancers · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2). We have now found that human PDAC tumors display higher levels of histone H3K9 and H3K27 acetylation in fibrotic regions. We show that relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels demonstrate increased histone H3K9 and H3K27 acetylation, along with increased expression of p300, PCAF and GCN5 histone acetyltransferases (HATs). Knocking down HMGA2 attenuates the effect of collagen on histone H3K9 and H3K27 acetylation and on collagen-induced p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 demonstrate increased histone H3K9 and H3K27 acetylation. Additionally, we show that cells in three-dimensional collagen gels demonstrate increased protection against gemcitabine. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs sensitizes the cells to gemcitabine in three-dimensional collagen. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance in vitro and identify HATs as potential therapeutic targets against this deadly cancer.
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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.