ArticleCell death and differentiation2023
Collagen I-DDR1 signaling promotes hepatocellular carcinoma cell stemness via Hippo signaling repression.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 48 citations in OpenAlex.
- YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by canonical driver gene mutations.Communications biology · 2026Article
- Interactions between circular RNAs (circRNAs) and the Hippo pathway in cancer.Molecular biology reports · 2026Review
- RNA methyltransferase NSUN5 promotes oral squamous cell carcinoma proliferation and migration by enhancing YAP1 expression in an m5C-dependent manner.Odontology · 2026Article
- DDR1 in esophageal squamous cell carcinoma: bioinformatics discovery and experimental validation.Translational cancer research · 2026Article
- Article
- Review
- Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma.Molecular biomedicine · 2026Article
- OSCAR functions as a collagen I receptor to suppress hippo signaling and reprogram lipid metabolism in clear-cell renal cell carcinoma.Cell death & disease · 2026Article
- Jianpi Jiedu Xiaozheng Fang Regulates Hepatocellular Carcinoma Proliferation and Metastasis Based on Network Pharmacology.Journal of cellular and molecular medicine · 2026Article
- Role ofInternational journal of molecular sciences · 2026Article
- Targeted DDR1 Treatment Strategy Enhances PD-1 Immunotherapy Efficacy against Gastric Cancer.Journal of medicinal chemistry · 2025Article
- Anti-metastatic potential of flavonoids for the treatment of cancers: focus on epithelial-mesenchymal transition (EMT) process.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- HOMER3 orchestrates SRC-YAP1 activity that promotes tumor cell growth and antagonizes anti-tumor immunotherapy in prostate cancer.Oncogene · 2025Article
- Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2025Article
- Cancer Stem Cells Connecting to Immunotherapy: Key Insights, Challenges, and Potential Treatment Opportunities.Cancers · 2025Review
- CD44 mediates the internalization of foot-and-mouth disease virus through macropinocytosis.Veterinary research · 2025Article
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- Overexpression ofJournal of biomedical research · 2025Article
- Synergistic approach to combating triple-negative breast cancer: DDR1-targeted antibody-drug conjugate combined with pembrolizumab.Journal of pharmaceutical analysis · 2025Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer stem cells (CSCs) are a minority population of cancer cells with stemness and multiple differentiation potentials, leading to cancer progression and therapeutic resistance. However, the concrete mechanism of CSCs in hepatocellular carcinoma (HCC) remains obscure. We found that in advanced HCC tissues, collagen I was upregulated, which is consistent with the expression of its receptor DDR1. Accordingly, high collagen I levels accompanied by high DDR1 expression are associated with poor prognoses in patients with HCC. Collagen I-induced DDR1 activation enhanced HCC cell stemness in vitro and in vivo. Mechanistically, DDR1 interacts with CD44, which acts as a co-receptor that amplifies collagen I-induced DDR1 signaling, and collagen I-DDR1 signaling antagonized Hippo signaling by facilitating the recruitment of PP2AA to MST1, leading to exaggerated YAP activation. The combined inhibition of DDR1 and YAP synergistically abrogated HCC cell stemness in vitro and tumorigenesis in vivo. A radiomic model based on T2 weighted images can noninvasively predict collagen I expression. These findings reveal the molecular basis of collagen I-DDR1 signaling inhibiting Hippo signaling and highlight the role of CD44/DDR1/YAP axis in promoting cancer cell stemness, suggesting that DDR1 and YAP may serve as novel prognostic biomarkers and therapeutic targets in HCC.
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