ArticleMolecular cancer therapeutics2017
Inhibition of Discoidin Domain Receptor 1 Reduces Collagen-mediated Tumorigenicity in Pancreatic Ductal Adenocarcinoma.
Article in Molecular cancer therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 119 citations in OpenAlex.
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- The DDR1 Tyrosine Kinase Promotes Th17 Cell Migration in Three-Dimensional Collagen and into the Joints During Inflammatory Arthritis.International journal of molecular sciences · 2026Article
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Inhibition of DDR1 potentiates carbon ion radiotherapy by promoting ferroptosis and immunogenic death in head and neck squamous cell carcinoma.Journal of translational medicine · 2025Article
- The type I collagen paradox in PDAC progression: microenvironmental protector turned tumor accomplice.Journal of translational medicine · 2025Review
- Fibrotic Fortresses and Therapeutic Frontiers: Pancreatic Stellate Cells and the Extracellular Matrix in Pancreatic Cancer.Cancer medicine · 2025Review
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Emerging strategies and translational advancements of DDR1 in oncology.Discover oncology · 2025Review
- Tumor-associated-fibrosis and active collagen-CD44 axis characterize a poor-prognosis subtype of gastric cancer and contribute to tumor immunosuppression.Journal of translational medicine · 2025Article
- Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models.Current medicinal chemistry · 2025Article
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFHistology and histopathology · 2024Article
- Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment.Cancers · 2024Review
- Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma.Journal of nanobiotechnology · 2024Article
- Progress of single-cell RNA sequencing combined with spatial transcriptomics in tumour microenvironment and treatment of pancreatic cancer.Journal of translational medicine · 2024Review
- Reprogramming the pancreatic cancer stroma and immune landscape by a silicasome nanocarrier delivering nintedanib, a protein tyrosine kinase inhibitor.Nano today · 2024Article
- Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2024Review
- Blockade of DDR1/PYK2/ERK signaling suggesting SH2 superbinder as a novel autophagy inhibitor for pancreatic cancer.Cell death & disease · 2023Article
- A network map of discoidin domain receptor 1(DDR1)-mediated signaling in pathological conditions.Journal of cell communication and signaling · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated protumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells. Pharmacologic inhibition of DDR1 with an ATP-competitive orally available small-molecule kinase inhibitor (7rh) abrogated collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduced colony formation and migration. Furthermore, the inhibition of DDR1 with 7rh showed striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors where it significantly reduced DDR1 activation and downstream signaling, reduced primary tumor burden, and improved chemoresponse. These data demonstrate that targeting collagen signaling in conjunction with conventional cytotoxic chemotherapy has the potential to improve outcome for pancreatic cancer patients.
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