ArticleJournal of gastroenterology2008
Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma.
Article in Journal of gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 119 citations in OpenAlex.
- Prognostic value of Wnt inhibitory factor-1 expression in hepatocellular carcinoma that is independent of gene methylation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2011Trial
- Integrating cell-free DNA methylation of SEPT9 and SFRP2 into a machine learning model for early diagnosis of HCC.Biomarkers in medicine · 2025Article
- Unraveling the Role of the Wnt Pathway in Hepatocellular Carcinoma: From Molecular Mechanisms to Therapeutic Implications.Journal of clinical and translational hepatology · 2025Review
- Expression, prognosis, immunological infiltration, and DNA methylation of members of the SFRP gene family in colorectal cancer: a comparative bioinformatic and experimental analysis.In vitro cellular & developmental biology. Animal · 2025Article
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- WNT/β-catenin signaling in hepatocellular carcinoma: The aberrant activation, pathogenic roles, and therapeutic opportunities.Genes & diseases · 2024Review
- scRNA-seq characterizing the heterogeneity of fibroblasts in breast cancer reveals a novel subtype SFRP4Frontiers in oncology · 2024Article
- Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.Frontiers in oncology · 2024Review
- Oncogenic Viruses and the Epigenome: How Viruses Hijack Epigenetic Mechanisms to Drive Cancer.International journal of molecular sciences · 2023Review
- Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.Cancers · 2022Review
- Identification of a DNA Damage Response and Repair-Related Gene-Pair Signature for Prognosis Stratification Analysis in Hepatocellular Carcinoma.Frontiers in pharmacology · 2022Article
- Tumor suppressor role of sFRP‑4 in hepatocellular carcinoma via the Wnt/β‑catenin signaling pathway.Molecular medicine reports · 2021Article
- Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis.Cancer metastasis reviews · 2021Review
- Wnt/β-Catenin Signaling in Oral Carcinogenesis.International journal of molecular sciences · 2020Review
- Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer.Clinical epigenetics · 2020Article
- Association between SFRP promoter hypermethylation and different types of cancer: A systematic review and meta-analysis.Oncology letters · 2019Article
- Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma.Cancers · 2018Article
- Oligomerization of Frizzled and LRP5/6 protein initiates intracellular signaling for the canonical WNT/β-catenin pathway.The Journal of biological chemistry · 2018Article
- Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Decreased expression of SFRP2 promotes development of the pituitary corticotroph adenoma by upregulating Wnt signaling.International journal of oncology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of the Wnt signaling pathway is frequently observed in hepatocellular carcinoma (HCC), though mutation of three of its components, CTNNB1, AXIN1, and AXIN2, is observed substantially less often.
methodsWe examined the relationship between Wnt signaling and epigenetic alteration of secreted frizzled-related protein (SFRP) genes in HCC.
resultsWe frequently detected the active form of beta-catenin and accumulation of nuclear beta-catenin in liver cancer cell lines. We detected methylation of SFRP family genes in liver cancer cell lines (SFRP1, 9/12, 75%; SFRP2, 7/12, 58%; SFRP4, 3/12, 25%; SFRP5, 7/12, 58%) and primary HCCs (SFRP1, 9/19, 47%; SFRP2, 12/19, 63%; SFRP5, 8/19, 42%), though methylation of SFRP4 was not found in primary HCCs. SFRP methylation also was detected in hepatitis B or C virus-associated chronic hepatitis (SFRP1, 6/37, 16%; SFRP2, 14/37, 38%; SFRP5, 5/37, 14%) and liver cirrhosis (SFRP1, 10/28, 36%; SFRP2, 9/28, 32%; SFRP5, 3/28, 11%), suggesting that methylation of these genes is an early event in liver carcinogenesis. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor (TCF/LEF) transcriptional activity in liver cancer cells, while overexpression of a beta-catenin mutant and depletion of SFRP1 using siRNA synergistically upregulated TCF/LEF transcriptional activity.
conclusionsOur results confirm the frequent methylation and silencing of Wnt antagonist genes in HCC, and suggest that their loss of function contributes to activation of Wnt signaling during hepatocarcinogenesis.
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Registered trials
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 OpenQuestion graph.