ArticleJournal of cancer research and clinical oncology2020
Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations.
Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Hepatoblastoma: an investigation of diagnostic, prognostic, and therapeutic gene targets and biomarkers.Pediatric research · 2026Pooled it
- ALKBH1 gene polymorphisms confer hepatoblastoma susceptibility in Chinese children.Scientific reports · 2026Article
- A novel Notch and WNT signaling mechanism contribute to paediatric DCM: a pathway to new therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Hepatoblastoma: From Molecular Mechanisms to Therapeutic Strategies.Current oncology (Toronto, Ont.) · 2025Review
- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- Concentration of Secreted Frizzled-Related Proteins (SFRPs) in Non-Small Cell Lung Carcinoma Subtypes-A Preliminary Study.Current oncology (Toronto, Ont.) · 2023Article
- Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment.Molecular cancer · 2023Review
- Review
- The Curious Case of the HepG2 Cell Line: 40 Years of Expertise.International journal of molecular sciences · 2021Review
- Development and validation of genomic and epigenomic signatures associated with tumor immune microenvironment in hepatoblastoma.BMC cancer · 2021Article
- Genetic and epigenetic basis of hepatoblastoma diversity.Nature communications · 2021Article
- miR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells.Journal of immunology research · 2021Article
- Hypoxic Non-Small-Cell Lung Cancer Cell-Secreted Exosomal microRNA-582-3p Drives Cancer Cell Malignant Phenotypes by Targeting Secreted Frizzled-Related Protein 1.Cancer management and research · 2020Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists. However, the role of the WNT inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed in pediatric liver cancer so far.
resultsIn our study, we investigated the gene expression level, DNA methylation status and functional relevance of SFRP1 in HB cell lines and in pediatric liver tumor patient samples. SFRP1 was downregulated due to DNA promoter methylation in all tested HB cell lines. Overexpression of SFRP1 in HB cell lines diminished tumor cell proliferation, colony formation and migration potential. In addition, the SFRP1-expressing HB cell lines showed reduced WNT/β-catenin signaling pathway activity and decreased expression of WNT target genes. To evaluate the utility of SFRP1 as a biomarker in pediatric liver cancer, we determined the gene expression level and DNA methylation status of SFRP1 in 45 pediatric liver tumor patient samples. The correlation analysis of different clinical parameters and tumor characteristics revealed a significant correlation of reduced SFRP1 expression with the presence of mutant β-catenin. The methylation status of SFRP1 was furthermore associated to a pediatric liver tumor type with HCC-like characteristics, TERT mutations and an older age at diagnosis.
conclusionAltogether, our data demonstrate that the epigenetic suppression of the WNT/β-catenin antagonist SFRP1 has an important impact on the malignant behavior of HB cells. Although SFRP1 methylation is a common event in HCC-like pediatric liver tumors, its potential as a prognostic or diagnostic biomarker needs to be further investigated.
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