Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of β-catenin in the liver
Abstract
To clarify molecular mechanisms underlying liver carcinogenesis induced by aberrant activation of Wnt pathway, we isolated the target genes of beta-catenin from mice exhibiting constitutive activated beta-catenin in the liver. Adenovirus-mediated expression of oncogenic beta-catenin was used to isolate early targets of beta-catenin in the liver. Suppression subtractive hybridization was used to identify the leukocyte cell-derived chemotaxin 2 (LECT2) gene as a direct target of beta-catenin. Northern blot and immunohistochemical analyses demonstrated that LECT2 expression is specifically induced in different mouse models that express activated beta-catenin in the liver. LECT2 expression was not activated in livers in which hepatocyte proliferation was induced by a beta-catenin-independent signal. We characterized by mutagenesis the LEF/TCF site, which is crucial for LECT2 activation by beta-catenin. We further characterized the chemotactic property of LECT2 for human neutrophils. Finally, we have shown an up-regulation of LECT2 in human liver tumors that expressed aberrant activation of beta-catenin signaling; these tumors constituted a subset of hepatocellular carcinomas (HCC) and most of the hepatoblastomas that were studied. In conclusion, our results show that LECT2, which encodes a protein with chemotactic properties for human neutrophils, is a direct target gene of Wnt/beta-catenin signaling in the liver. Since HCC develops mainly in patients with chronic hepatitis or cirrhosis induced by viral or inflammatory factors, understanding the role of LECT2 in liver carcinogenesis is of interest and may lead to new therapeutic perspectives.
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LECT2 functions in liver regeneration, immune modulation, bone growth, neural development, glucose metabolism, metabolic syndrome, and cancer.
“LECT2 functions in liver regeneration, immune modulation, bone growth, neural development, glucose metabolism, metabolic syndrome, and cancer [[241], [242], [243], [244], [245], [246]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [243]
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Hepatokines and metabolism: Deciphering communication from the liver
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- Authors
- Ovejero, C., Cavard, C., Périanin, A., Hakvoort, T., Vermeulen, J., Godard, C., Fabre, M., Chafey, P., Suzuki, K., Romagnolo, B., Yamagoe, S., & Perret, C.
- Affiliations
- Institut Cochin (FR)
- Amsterdam UMC Location University of Amsterdam (NL)
- National Institute of Infectious Diseases (JP)
- Corresponding author
- Perret, Christine
- Venue
- Hepatology
- Published
- 2004-07
- Volume
- 40
- Issue
- 1
- Pages
- 167-176
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2062371609
- Cited by
- 118
- References
- 33
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 4
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Comité de Paris de la Ligue Nationale contre le Cancer
- Association pour la Recherche contre le Cancer
- Ministère Délégué à la Recherche et aux Nouvelles Technologies, ACI Biologie de Développement et Physiologie Intégrative
- La Ligue Nationale contre le Cancer
- 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
- LECT2, β-catenin, Wnt/β-catenin signaling, hepatocarcinogenesis, hepatocellular carcinoma, hepatoblastoma, direct target genes, neutrophil chemotaxis, liver tumors
- MeSH terms
- Transcription Factor 4, Animals, Cell Line, Chemotaxis, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Liver Neoplasms, Mice, Inbred Strains, Mice, Transgenic, Nerve Tissue Proteins, Neutrophils, Nucleic Acid Hybridization, Transcription Factors, Signal Transduction, Trans-Activators, Up-Regulation, Gene Expression, Intercellular Signaling Peptides and Proteins, beta Catenin, Mice, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
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