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Cited by 215Wnt/β-catenin signaling in development and cancerLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

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Bengochea, A, de Souza, M M, Lefrançois, L, Le Roux, E, Galy, O, Chemin, I, Kim, M, Wands, J R +5 more·2008·British Journal of Cancer
DOI 10.1038/sj.bjc.6604422PMC PMC2453022
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Abstract

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the beta-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT-PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (beta-catenin, protein kinase C, and C-Jun NH(2)-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis.

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  • Five activating alterations in Wnt-TGFβ-class (FZD7, FZD6, TCF4, FRAT2 and ARBB2) have been related to Wnt activation in cancer.

    “among which five of them (FZD7, FZD6, TCF4, FRAT2 and ARBB2) have been related to Wnt activation in cancer (20-25)”

    From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [20]

    The Abstract reports FZD7 and FZD6 upregulation in hepatocellular carcinoma associated with activation of potentially FZD-dependent pathways. The Discussion says FZD7 can activate canonical Wnt signaling but that the evidence for FZD6 is less clear. The paper does not establish activating alterations in TCF4, FRAT2, or ARBB2, so it does not support the full five-gene claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several genes dysregulated in Wnt-TGFβ-class characterize Wnt-signaling activation in cancer.

    “In contrast, several genes dysregulated in Wnt-TGFβ-class characterize Wnt-signaling activation in cancer (20-25) (Fig. 6).”

    From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [20]

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Research works printed but not linked: 38

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Authors
Bengochea, A., de Souza, M. M., Lefrançois, L., Le Roux, E., Galy, O., Chemin, I., Kim, M., Wands, J. R., Trepo, C., Hainaut, P., Scoazec, J.-Y., Vitvitski, L., & Merle, P.
Affiliations
  • Lyon 1 Université (FR)
  • Brown University (US)
  • Centre international de recherche sur le cancer (FR)
  • Hospices Civils de Lyon (FR)
Corresponding author
Merle, P
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2008-06-24
Volume
99
Issue
1
Pages
143-150
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/sj.bjc.6604422
PMC
PMC2453022
OpenAlex
W2059509996
Cited by
215
References
40
Citations by year
2026: 4 · 2025: 8 · 2024: 13 · 2023: 8 · 2022: 16 · 2021: 11 · 2020: 12 · 2019: 17 · 2018: 9 · 2017: 16 · 2016: 12 · 2015: 16 · 2014: 13 · 2013: 11 · 2012: 13
FWCI
4.94
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Cancer (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Agence Nationale de la Recherche
  • Institut National de la Santé et de la Recherche Médicale
  • National Institutes of Health (CA-35711, RR15578)
  • National Institute on Alcohol Abuse and Alcoholism (AA-02066)
  • National Cancer Institute (R37CA035711, R01CA035711, CA 35711)
  • National Center for Research Resources (P20RR 15578, P20RR015578)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
hepatocellular carcinoma, Frizzled receptors, β-catenin signaling, protein kinase C, c-Jun NH2-kinase, hepatocarcinogenesis, hepatitis B virus, liver fibrosis, tumor differentiation, hepatocytes
MeSH terms
Gene Expression Regulation, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Cell Line, Tumor, Frizzled Receptors

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