ArticleJournal of experimental & clinical cancer research : CR2015
DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 98 citations in OpenAlex.
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- DDR2 ameliorates nonalcoholic hepatic steatosis by activating the AMPK/ACC pathway.Scientific reports · 2026Article
- Drug repositioning of regorafenib for renal cell carcinoma identifiesThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review).Oncology letters · 2025Review
- Discoidin Domain Receptor 2 (DDR2) Promotes Prostate Cancer Progression in Cooperation with Collagen Remodeling.Acta histochemica et cytochemica · 2025Article
- STAT3-mediated upregulation of TRIM6 promotes hepatocellular carcinoma invasion through the DDX58-Snail1 axis.Scientific reports · 2025Article
- Ankrd1 Promotes Lamellipodia Formation and Cell Motility via Interaction with Talin-1 in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Article
- Transient intracellular expression of PD-L1 and VEGFR2 bispecific nanobody in cancer cells inspires long-term T cell activation and infiltration to combat tumor and inhibit cancer metastasis.Molecular cancer · 2025Article
- Control of Snail1 protein stability by post-translational modifications: the basis for a complex regulation of Snail1 function.International journal of biological sciences · 2025Review
- Oncogenic mechanisms of COL10A1 in cancer and clinical challenges (Review).Oncology reports · 2024Review
- Fibrosis and Hepatocarcinogenesis: Role of Gene-Environment Interactions in Liver Disease Progression.International journal of molecular sciences · 2024Review
- DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression.Oncogene · 2024Article
- MicroRNA-143 acts as a tumor suppressor through Musashi-2/DLL1/Notch1 and Musashi-2/Snail1/MMPs axes in acute myeloid leukemia.Journal of translational medicine · 2023Article
- LncRNA CEBPA-DT promotes liver cancer metastasis through DDR2/β-catenin activation via interacting with hnRNPC.Journal of experimental & clinical cancer research : CR · 2022Article
- Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis.Journal of cancer research and clinical oncology · 2022Article
- DDR2 coordinates EMT and metabolic reprogramming as a shared effector of FOXQ1 and SNAI1.Cancer research communications · 2022Article
- Article
- Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation.Oncogene · 2022Article
- The portrait of liver cancer is shaped by mitochondrial genetics.Cell reports · 2022Article
- COL10A1-DDR2 axis promotes the progression of pancreatic cancer by regulating MEK/ERK signal transduction.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear.
methodsDDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed.
resultsDDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells.
conclusionsOur findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC.
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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.