ArticleCellular oncology (Dordrecht, Netherlands)2022
Discoidin domain receptor 1 promotes hepatocellular carcinoma progression through modulation of SLC1A5 and the mTORC1 signaling pathway.
Article in Cellular oncology (Dordrecht, Netherlands), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanisms of DDR1 in Reinforcing the Resistance to Radiotherapy in Breast Cancer Through the AMPK/SIRT1/PGC-1α Pathway.Biochemical genetics · 2026Article
- Regulation of Amino Acid Transporters by Cell Surface Receptors.Antioxidants (Basel, Switzerland) · 2026Review
- Unveiling membrane transporter proteins-related genes for predicting the prognosis of hepatocellular carcinoma patients.Discover oncology · 2026Article
- Comprehensive characterization of SLC41A3 identifies it as an immune-related prognostic biomarker and therapeutic target in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Neutrophil Extracellular Traps in Pancreatic Ductal Adenocarcinoma: A Vicious Cycle in the Tumor Microenvironment and Targeted Interventions.International journal of biological sciences · 2026Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Targeted DDR1 Treatment Strategy Enhances PD-1 Immunotherapy Efficacy against Gastric Cancer.Journal of medicinal chemistry · 2025Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- Emerging strategies and translational advancements of DDR1 in oncology.Discover oncology · 2025Review
- KLF7 Promotes Hepatocellular Carcinoma Progression Through Regulating SLC1A5-Mediated Tryptophan Metabolism.Journal of cellular and molecular medicine · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review.Journal of clinical and translational hepatology · 2023Review
- Cellular senescence throws new insights into patient classification and pharmacological interventions for clinical management of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2023Article
- Collagen I-DDR1 signaling promotes hepatocellular carcinoma cell stemness via Hippo signaling repression.Cell death and differentiation · 2023Article
- Ferroptosis-Related Gene SLC1A5 Is a Novel Prognostic Biomarker and Correlates with Immune Microenvironment in HBV-Related HCC.Journal of clinical medicine · 2023Article
- Focusing on discoidin domain receptors in premalignant and malignant liver diseases.Frontiers in oncology · 2023Review
- Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Formyl-Peptide Receptor 2 Signaling Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming of Lung Cancer Cells.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHepatocellular carcinoma (HCC) is one of the most common cancers in the world with a high mortality rate. Receptor tyrosine kinases play important roles in the occurrence and development of various cancers. Discoid protein domain receptor 1 (DDR1) is a special type of transmembrane receptor tyrosine kinase. Here, we show that the expression of DDR1 is significantly increased in HCC and is related to a poor clinical prognosis.
methodsThe expression of DDR1 in HCC cell lines and primary HCC specimens was evaluated using Western blotting and immunohistochemistry. A correlation between DDR1 and SLC1A5 expression was also investigated in primary HCC specimens. Cell proliferation was evaluated using in vitro CCK8 and colony formation assays. Gene knock-down and overexpression assays, CHX, NH
resultsWe found that DDR1 promotes the proliferation of HCC cells and accelerates the growth of HCC tumor xenografts, while DDR1 downregulation had the opposite effect. We also found that loss or gain of DDR1 expression affected HCC cell cycle progression. Mechanistically, we found that DDR1 interacts with SLC1A5, which belongs to the solute carrier (SLC) family of transporters, and regulates its stability, thereby affecting the mTORC1 signaling pathway. In addition, we found that SLC1A5 regulation by DDR1 can be restored by lysosome inhibitors. We also found that DDR1 is highly expressed in HCC tissues and that increased DDR1 expression predicts a shorter overall survival (OS) time. We additionally found that the expression of SLC1A5 was positively correlated with that of DDR1. Together, our data indicate that DDR1 acts as a tumor-promoting factor that can control HCC cell proliferation and cell cycle progression by stabilizing SLC1A5 in a lysosome-dependent way.
conclusionsOur study reveals a new mechanism by which DDR1 plays a liver cancer-promoting role. We also found that DDR1 expression serves as an independent prognostic marker, and that DDR1 and SLC1A5 expression levels are positively correlated in clinical samples. Our findings provide a new perspective for understanding HCC development and offers new targets for the treatment and management of HCC.
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