ArticlePloS one2008
A cryptic frizzled module in cell surface collagen 18 inhibits Wnt/beta-catenin signaling.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 60 citations in OpenAlex.
- Specific collagen XVIII isoforms promote adipose tissue accrual via mechanisms determining adipocyte number and affect fat deposition.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
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- Heparan sulfate chains in hepatocellular carcinoma.Gastroenterology report · 2025Review
- Comparative Transcriptome Analysis of the Hypothalamic-Pituitary-Gonadal Axis of Jinhu Grouper (Genes · 2024Article
- Comment on: "Wnt Binding Affinity Prediction for Putative Frizzled-Type Cysteine-Rich Domains".International journal of molecular sciences · 2019Article
- Basement membrane collagens and disease mechanisms.Essays in biochemistry · 2019Review
- Wnt Binding Affinity Prediction for Putative Frizzled-Type Cysteine-Rich Domains.International journal of molecular sciences · 2019Article
- 2,3,7,8 Tetrachlorodibenzo-p-dioxin-induced RNA abundance changes identify Ackr3, Col18a1, Cyb5a and Glud1 as candidate mediators of toxicity.Archives of toxicology · 2017Article
- De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas.Oncotarget · 2016Article
- Proteoglycans in liver cancer.World journal of gastroenterology · 2016Review
- The rs3957357C>T SNP in GSTA1 Is Associated with a Higher Risk of Occurrence of Hepatocellular Carcinoma in European Individuals.PloS one · 2016Article
- Wnt3a: functions and implications in cancer.Chinese journal of cancer · 2015Review
- Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.Archives of toxicology · 2013Review
- Analysis of the transcriptome of differentiating and non-differentiating preadipocytes from rats and humans by next generation sequencing.Molecular and cellular biochemistry · 2012Article
- Article
- Fibronectin and beta-catenin act in a regulatory loop in dermal fibroblasts to modulate cutaneous healing.The Journal of biological chemistry · 2011Article
- Extracellular matrix dynamics in hepatocarcinogenesis: a comparative proteomics study of PDGFC transgenic and Pten null mouse models.PLoS genetics · 2011Article
- Lack of collagen XVIII long isoforms affects kidney podocytes, whereas the short form is needed in the proximal tubular basement membrane.The Journal of biological chemistry · 2011Article
- Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active β-catenin.Oncogene · 2011Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagens contain cryptic polypeptide modules that regulate major cell functions, such as cell proliferation or death. Collagen XVIII (C18) exists as three amino terminal end variants with specific amino terminal polypeptide modules. We investigated the function of the variant 3 of C18 (V3C18) containing a frizzled module (FZC18), which carries structural identity with the extracellular cysteine-rich domain of the frizzled receptors. We show that V3C18 is a cell surface heparan sulfate proteoglycan, its topology being mediated by the FZC18 module. V3C18 mRNA was expressed at low levels in 21 normal adult human tissues. Its expression was up-regulated in fibrogenesis and in small well-differentiated liver tumors, but decreased in advanced human liver cancers. Low FZC18 immunostaining in liver cancer nodules correlated with markers of high Wnt/beta-catenin activity. V3C18 (M(r) = 170 kD) was proteolytically processed into a cell surface FZC18-containing 50 kD glycoprotein precursor that bound Wnt3a in vitro through FZC18 and suppressed Wnt3a-induced stabilization of beta-catenin. Ectopic expression of either FZC18 (35 kD) or its 50 kD precursor inhibited Wnt/beta-catenin signaling in colorectal and liver cancer cell lines, thus downregulating major cell cycle checkpoint gatekeepers cyclin D1 and c-myc and reducing tumor cell growth. By contrast, full-length V3C18 was unable to inhibit Wnt signaling. In summary, we identified a cell-surface signaling pathway whereby FZC18 inhibits Wnt/beta-catenin signaling. The signal, encrypted within cell-surface C18, is released by enzymatic processing as an active frizzled cysteine-rich domain (CRD) that reduces cancer cell growth. Thus, extracellular matrix controls Wnt signaling through a collagen-embedded CRD behaving as a cell-surface sensor of proteolysis, conveying feedback cues to control cancer cell fate.
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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.