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Both tumor types exhibit genetic and epigenetic alterations in the WNT\/\u03b2-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of \u03b2-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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In 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. <jats:italic>SFRP1<\/jats:italic> was downregulated due to DNA promoter methylation in all tested HB cell lines. Overexpression of <jats:italic>SFRP1<\/jats:italic> in HB cell lines diminished tumor cell proliferation, colony formation and migration potential. In addition, the SFRP1-expressing HB cell lines showed reduced WNT\/\u03b2-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 <jats:italic>SFRP1<\/jats:italic> in 45 pediatric liver tumor patient samples. The correlation analysis of different clinical parameters and tumor characteristics revealed a significant correlation of reduced <jats:italic>SFRP1<\/jats:italic> expression with the presence of mutant \u03b2-catenin. The methylation status of <jats:italic>SFRP1<\/jats:italic> was furthermore associated to a pediatric liver tumor type with HCC-like characteristics, <jats:italic>TERT<\/jats:italic> mutations and an older age at diagnosis.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Altogether, our data demonstrate that the epigenetic suppression of the WNT\/\u03b2-catenin antagonist <jats:italic>SFRP1<\/jats:italic> has an important impact on the malignant behavior of HB cells. Although <jats:italic>SFRP1<\/jats:italic> methylation is a common event in HCC-like pediatric liver tumors, its potential as a prognostic or diagnostic biomarker needs to be further investigated.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00432-020-03182-1","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T16:03:46Z","timestamp":1584547426000},"page":"1153-1167","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations"],"prefix":"10.1007","volume":"146","author":[{"given":"Ivonne","family":"Regel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Eichenm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujjwal Mukund","family":"Mahajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Hagl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Benitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"H\u00e4berle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vokuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"von Schweinitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kappler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"issue":"29","key":"3182_CR1","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.1038\/sj.onc.1209439","volume":"25","author":"O Aguilera","year":"2006","unstructured":"Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, Espada J et al (2006) Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. 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