p53 mutation as a source of aberrant β-catenin accumulation in cancer cells
Open accessAbstract
beta-catenin is involved in both cell-cell interactions and wnt pathway-dependent cell fate determination through its interactions with E-cadherin and TCF/LEF transcription factors, respectively. Cytoplasmic/nuclear levels of beta-catenin are important in regulated transcriptional activation of TCF/LEF target genes. Normally, these levels are kept low by proteosomal degradation of beta-catenin through Axin1- and APC-dependent phosphorylation by CKI and GSK-3beta. Deregulation of beta-catenin degradation results in its aberrant accumulation, often leading to cancer. Accordingly, aberrant accumulation of beta-catenin is observed at high frequency in many cancers. This accumulation correlates with either mutational activation of CTNNB1 (beta-catenin) or mutational inactivation of APC and Axin1 genes in some tumors. However, there are many tumors that display beta-catenin accumulation in the absence of a mutation in these genes. Thus, there must be additional sources for aberrant beta-catenin accumulation in cancer cells. Here, we provide experimental evidence that wild-type beta-catenin accumulates in hepatocellular carcinoma (HCC) cells in association with mutational inactivation of p53 gene. We also show that worldwide p53 and beta-catenin mutation rates are inversely correlated in HCC. These data suggest that inactivation of p53 is an important cause of aberrant accumulation of beta-catenin in cancer cells.
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Huh7 and SNU387 have no known mutations in β-catenin or other Wnt-related genes.
“Huh7 and SNU387 have no known mutations in β-catenin or other Wnt-related gens (27, 28).”
From Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib (2012) · cites this paper as [28]
The Comparative analysis section reports wild-type β-catenin in both Huh7 and SNU387. The Discussion reports no Axin1 mutation in Huh7 and says none was identified in the remaining nine cell lines, which includes SNU387. The paper does not establish the absence of mutations in all other Wnt-related genes in these two lines. (LLM, conf=0.85)
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The IARC TP53 database: new online mutation analysis and recommendations to users
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Lachenmayer, A., Alsinet, C., Savic, R., Cabellos, L., Toffanin, S., Hoshida, Y., Villanueva, A., Minguez, B., Newell, P., Tsai, H.-W., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2322 · Cited by 306 · see citing works
Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells
Yuzugullu, H., Benhaj, K., Ozturk, N., Senturk, S., Celik, E., Toylu, A., Tasdemir, N., Yilmaz, M., Erdal, E., Akcali, K. C., et al. (2009) · Molecular Cancer · doi:10.1186/1476-4598-8-90 · Cited by 215 · see citing works
- Authors
- Cagatay, T., & Ozturk, M.
- Venue
- Oncogene
- Published
- 2002-11-13
- Volume
- 21
- Issue
- 52
- Pages
- 7971-7980
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2025995411
- Cited by
- 110
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 3 · 2021: 11 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oncogene (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bilkent University Institutional Repository (Bilkent University) (submittedVersion, cc-by)
- Funders
- Bilkent Üniversitesi
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- TP53 mutation, beta-catenin accumulation, hepatocellular carcinoma, Wnt signaling, TCF/LEF transcription factors, AXIN1, APC, GSK3β, proteasomal degradation, E-cadherin, tumor suppressor inactivation, mutation rate
- MeSH terms
- Cytoskeletal Proteins, Humans, Liver Neoplasms, Mutation, Tumor Cells, Cultured, Trans-Activators, Tumor Suppressor Protein p53, beta Catenin
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