ArticleJournal of translational medicine2023
The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Cancer-associated fibroblast-derived extracellular vesicles facilitate metastasis in hepatocellular carcinoma by delivering CTGF.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Senescent fibroblasts secrete CTHRC1 to promote cancer stemness in hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Article
- Unlocking the Role of OCT4 in Cancer Lineage Plasticity: A Cross-Cancer Perspective with an Emphasis on Prostate Cancer.Biomedicines · 2025Review
- Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.Cell death and differentiation · 2025Article
- STC1 encapsulated in small extracellular vesicles from laryngeal squamous cell carcinoma cells induces CD8Cancer immunology, immunotherapy : CII · 2025Article
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Stanniocalcin-1 in tumor immunity: acts via macrophages.Frontiers in immunology · 2024Review
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.Oncology reports · 2024Article
- Comprehensive analysis for the immune related biomarkers of platinum-based chemotherapy in ovarian cancer.Translational oncology · 2023Article
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis.Journal of translational medicine · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer-associated fibroblasts (CAFs), an important component of the tumor microenvironment (TME), play crucial roles in tumor stemness. It has been shown in various cancer studies that stanniocalcin-1 (STC1) is secreted by CAFs, however, its function in HCC is still not clear.
methodsThe serum concentration and intracellular expression level of STC1 were quantified by ELISA and western blotting, respectively. The role of CAF-derived STC1 in HCC stemness was investigated by sphere formation, sorafenib resistance, colony formation, and transwell migration and invasion assays in vitro and in an orthotopic liver xenograft model in vivo. An HCC tissue microarray containing 72 samples was used to evaluate the expression of STC1 and Notch1 in HCC tissues. Coimmunoprecipitation (CoIP) and dual-luciferase reporter assays were performed to further explore the underlying mechanisms. ELISAs were used to measure the serum concentration of STC1 in HCC patients.
resultsWe demonstrated that CAFs were the main source of STC1 in HCC and that CAF-derived STC1 promoted HCC stemness through activation of the Notch signaling pathway. In HCC patients, the expression of STC1 was positively correlated with Notch1 expression and poor prognosis. The co-IP assay showed that STC1 directly bound to Notch1 receptors to activate the Notch signaling pathway, thereby promoting the stemness of HCC cells. Our data further demonstrated that STC1 was a direct transcriptional target of CSL in HCC cells. Furthermore, ELISA revealed that the serum STC1 concentration was higher in patients with advanced liver cancer than in patients with early liver cancer.
conclusionsCAF-derived STC1 promoted HCC stemness via the Notch1 signaling pathway. STC1 might serve as a potential biomarker for the prognostic assessment of HCC, and the stromal-tumor amplifying STC1-Notch1 feedforward signal could constitute an effective therapeutic target for HCC patients.
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