Knockdown of apoptosis signal-regulating kinase 1 modulates basal glycogen synthase kinase-3 beta kinase activity and regulates cell migration

Abstract

GSK-3 beta is a basally active kinase. Axin forms a complex with GSK-3 beta and beta-catenin; this complex promotes the GSK-3 beta-dependent phosphorylation of beta-catenin, thereby inducing its degradation. However, the inhibition of GSK-3 beta provokes cell migration via the dysregulation of b-catenin. In this study, we determined that the level of apoptosis signal-regulating kinase 1 (ASK1) was lower in a metastatic breast cancer cell line, compared to that of non-metastatic cancer cell lines and the knockdown of ASK1 not only induces b-catenin activation via the inhibition of GSK-3 beta and collapsing the subsequent protein complex by regulating Axin dynamics, but also stimulates cell migration. Together, the blockage of the GSK-3 beta-beta-catenin pathway resulting from the knockdown of ASK1 modulates the migration of breast cancer cells. (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.