β-catenin mutation and overexpression in hepatocellular carcinoma

Wong, Chun Ming; Fan, Sheung Tat; Ng, Irene Oi–Lin

doi:10.1002/1097-0142(20010701)92:1<136::aid-cncr1301>3.0.co;2-r

Cited by 336 publications

(299 citation statements)

References 28 publications

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“…However, mutations of β-catenin and/or APC genes are detected only in 20-30%, whereas axin1 mutations are rare in HCC [18,[33][34][35][36][37][38]. Previous reports suggest that several signaling components upstream of β-catenin may be involved for wild-type β-catenin accumulation to occur in HCC.…”

Section: Discussionmentioning

confidence: 99%

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Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Kim¹,

Lee²,

Tsedensodnom³

et al. 2008

Journal of Hepatology

171

173

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Background/Aims-The canonical Wnt signaling is frequently activated in human hepatocellular carcinoma (HCC). We previously demonstrated that up-regulation of Frizzled-7 receptor (FZD7) in HCC was associated with nuclear accumulation of wild-type β-catenin. Here, we investigated Wnt ligand(s) that may activate the Wnt/β-catenin pathway through FZD7 in HCC cells. Results-In hepatitis B virus (HBV)-induced HCC, Wnt3 was upregulated in tumor and peritumoral tissues compared to normal liver and downstream β-catenin target genes were also increased in these samples. Activation of the Wnt/β-catenin pathway in FOCUS-Wnt3 cells was demonstrated by β-catenin accumulation, enhanced TCF transcriptional activity and proliferation rate. The activation of Wnt/β-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA. More important, a specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, which suggest that the action of Wnt3 was mediated via FZD7. Methods-To identifyConclusions-These findings demonstrate a functional interaction between Wnt3 and FZD7 leading to activation of the Wnt/β-catenin signaling pathway in HCC cells and may play a role during hepatocarcinogenesis.

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Section: Discussionmentioning

confidence: 99%

“…Exon 3 mutations of the β-catenin gene from these HCC and peritumoral tissues were analyzed by a previous method [18]. Four normal liver tissues were obtained from individuals who had undergone hepatic resection for single metastasis of colorectal cancer to the liver and served as controls.…”

Section: Human Hcc Tissues and Cell Linesmentioning

confidence: 99%

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Kim¹,

Lee²,

Tsedensodnom³

et al. 2008

Journal of Hepatology

171

173

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“…Depending on the study in 17-40% of human HCCs exhibit a nuclear accumulation of b-catenin (Nhieu et al, 1999;Hsu et al, 2000;Wong et al, 2001;Prange et al, 2003). Somatic APC mutations, which lead to an aberrant concentration of b-catenin, as shown in, for example, colon carcinomas (Ficari et al, 2000), have seldom been described in HCCs.…”

Section: Signaling Pathways and Their Dysregulationmentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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“…However, this result has to be confirmed in a second study. Finally, b-catenin-activating mutations were found most frequently in large sized Wong et al, 2001) and well-differentiated tumors (Mao et al, 2001). Although the pathological tumor-node-metastasis staging has been applied clinically to HCC patients, this system is inadequate for predicting recurrence in individuals who undergo hepatic resection.…”

Section: Genetics Of Hepatocellular Tumors P Laurent-puig and J Zucmamentioning

confidence: 99%

Genetics of hepatocellular tumors

2006

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Numerous genetic alterations are accumulated during the process of hepatocarcinogenesis. These genetic alterations can be divided into two groups. The first set of genetic alterations is specific of hepatocellular tumor risk factors. It includes integration of hepatitis B virus (HBV) DNA, R249S TP53 (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations related to vinyl chloride exposure, hepatocyte nuclear factor 1a (HNF1a) mutations associated to hepatocellular adenomas and adenomatosis polyposis coli (APC) germline mutations predisposing to hepatoblastomas. The second set of genetic alterations are etiological nonspecific, it includes recurrent gains and losses of chromosomes, alteration of TP53 gene, activation of WNT/b-catenin pathway through CTNNB1/b-catenin and AXIN (axis inhibition protein) mutations, inactivation of retinoblastoma and IGF2R (insulin-like growth factor 2 receptor) pathways through inactivation of RB1 (retinoblastoma 1), P16 and IGF2R. Comprehensive analyses of these genetic alterations have defined two pathways of hepatocarcinogenesis according to the presence or the absence of chromosomal instability. Hepatitis B virus and poorly differentiated tumors are related to chromosome instable tumors associated with frequent TP53 mutations, whereas non-HBV and well-differentiated tumors are related to chromosomal stable samples that are frequently b-catenin activated. These classifications have clinical relevance as genetic alterations may also be related to prognosis.

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β-catenin mutation and overexpression in hepatocellular carcinoma

Cited by 336 publications

References 28 publications

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/β-catenin signaling pathway in hepatocellular carcinoma cells

Dysregulation of growth factor signaling in human hepatocellular carcinoma

Genetics of hepatocellular tumors

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