Dataset Information
Diverse Basis of ?-Catenin Activation in Human Hepatocellular Carcinoma: Implications in Biology and Prognosis.
Ontology highlight
ABSTRACT: Aim
?-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since ?-catenin phosphorylation by glycogen synthase kinase 3? (GSK3?) and casein kinase 1? (CK1?) results in its degradation, mutations affecting these phosphorylation sites cause ?-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of ?-catenin activation in human HCC.Methods
Gene alteration in exon3 of CTNNB1, gene expression of ?-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of ?-catenin were examined in 125 human HCC tissues.Results
Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described ?-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of ?-catenin target genes. Nuclear localization of ?-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear ?-catenin localization, loss of described ?-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001).Conclusion
This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to ?-catenin activation in human HCC. Additionally, the mechanism of nuclear ?-catenin localization without upregulation of described ?-catenin target genes might be of clinical importance depending on distinct mechanism.
SUBMITTER: Okabe H
PROVIDER: S-EPMC4839611 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Diverse Basis of β-Catenin Activation in Human Hepatocellular Carcinoma: Implications in Biology and Prognosis.
PloS one 20160421 4
<h4>Aim</h4>β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical ...[more]
