ArticleSignal transduction and targeted therapy2021
Activation of transmembrane receptor tyrosine kinase DDR1-STAT3 cascade by extracellular matrix remodeling promotes liver metastatic colonization in uveal melanoma.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 81 citations in OpenAlex.
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- Fatty Acid-Binding Protein 5 Potentially Regulates the Proliferation and Metastasis of Uveal Melanoma Cells Through the PI3K/AKT/mTOR Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- CDK6/4 inactivates BAP1 deubiquitinase destabilizing VHL to promote metastatic colonization in liver.Molecular cancer · 2026Article
- Research on the molecular mechanism of celastrol targeting CTNNB1/STAT3 to inhibit uveal melanoma based on network pharmacology and multi-omics analysis.Scientific reports · 2026Article
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- Multi-omics insights into SERPINE2-driven post-metastatic microenvironmental reprogramming in advanced cancers: implications for molecular targeting and immunotherapy.Frontiers in immunology · 2026Review
- Dual roles of DDR1 in stromal remodeling and immune escape: a regulator of the tumor immune microenvironment.Frontiers in immunology · 2026Review
- Charting the growth of programmed cell death studies in uveal melanoma: a bibliometric evidence.Discover oncology · 2025Article
- Extracellular Matrix Stiffness Regulates Cancer Stemness in Uveal Melanoma via the PIEZO1-DOT1L Axis.Investigative ophthalmology & visual science · 2025Article
- Comprehensive molecular analysis of uveal melanoma identifies targets in tumor-intrinsic and tumor-extrinsic pathways.iScience · 2025Article
- Thrombospondin 2 drives liver metastasis in skin cutaneous melanoma via regulation of angiogenesis and extracellular matrix remodeling.Melanoma research · 2025Article
- Effects of solamargine in hepatic metastasis of colorectal cancer: induction of ferroptosis and elimination of cancer stem cells.Chinese medicine · 2025Article
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- Overexpression ofJournal of biomedical research · 2025Article
- Emerging strategies and translational advancements of DDR1 in oncology.Discover oncology · 2025Review
- Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lactate supports cell-autonomous ECM production to sustain metastatic behavior in prostate cancer.EMBO reports · 2024Article
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures.Cellular oncology (Dordrecht, Netherlands) · 2024Article
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12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colonization is believed a rate-limiting step of metastasis cascade. However, its underlying mechanism is not well understood. Uveal melanoma (UM), which is featured with single organ liver metastasis, may provide a simplified model for realizing the complicated colonization process. Because DDR1 was identified to be overexpressed in UM cell lines and specimens, and abundant pathological deposition of extracellular matrix collagen, a type of DDR1 ligand, was noted in the microenvironment of liver in metastatic patients with UM, we postulated the hypothesis that DDR1 and its ligand might ignite the interaction between UM cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver. We tested this hypothesis and found that DDR1 promoted these malignant cellular phenotypes and facilitated metastatic colonization of UM in liver. Mechanistically, UM cells secreted TGF-β1 which induced quiescent hepatic stellate cells (qHSCs) into activated HSCs (aHSCs) which secreted collagen type I. Such a remodeling of extracellular matrix, in turn, activated DDR1, strengthening survival through upregulating STAT3-dependent Mcl-1 expression, enhancing stemness via upregulating STAT3-dependent SOX2, and promoting clonogenicity in cancer cells. Targeting DDR1 by using 7rh, a specific inhibitor, repressed proliferation and survival in vitro and in vivo outgrowth. More importantly, targeting cancer cells by pharmacological inactivation of DDR1 or targeting microenvironmental TGF-β1-collagen I loop exhibited a prominent anti-metastasis effect in mice. In conclusion, targeting DDR1 signaling and TGF-β signaling may be a novel approach to diminish hepatic metastasis in UM.
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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 Socratic graph.