The aurora kinase A regulates GSK-3β in gastric cancer cells
作者： A A Dar , A Belkhiri , W El-Rifai
DOI: 10.1038/ONC.2008.434
关键词:
摘要: Aurora kinase A (AURKA) is located at 20q13, a region that frequently amplified in gastric cancer. In this study, we have investigated the role of AURKA regulating glycogen synthase (GSK)-3β and β-catenin/TCF complex cancer cells. Our results demonstrate significant increase phosphorylation GSK-3β Ser 9 following overexpression AGS The immunoprecipitation with antibodies specific for indicated two proteins coexist same protein complex. recombinant human phosphorylated concentration-dependent manner, vitro. β-catenin (Ser33/37/Thr41) by known to target towards degradation. line our findings, phospho-GSK-3β level was accompanied decrease accumulation protein. knockdown reversed levels. immunofluorescence analysis demonstrated colocalization nuclear levels cells overexpressing AURKA. transcription activity measured using pTopFlash its mutant pFopFlash luciferase reporter vectors. Indeed, led activity, whereas dead (D274A) had no effect. Consistent these detected mRNA up-regulation several direct targets (cyclin D1, c-MYC, c-MYC-binding protein, CLDN1, FGF18 vascular endothelial growth factor), two-fold proliferation rate We conclude AURKA/GSK-3β interaction important β-catenin, underscoring novel oncogenic potential tumorigenesis.
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