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

Abstract

GSK-3β is a basally active kinase. Axin forms a complex with GSK-3β and β-catenin; this complex promotes the GSK-3β-dependent phosphorylation of β-catenin, thereby inducing its degradation. However, the inhibition of GSK-3β provokes cell migration via the dysregulation of β-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 β-catenin activation via the inhibition of GSK-3β and collapsing the subsequent protein complex by regulating Axin dynamics, but also stimulates cell migration. Together, the blockage of the GSK-3β-β-catenin pathway resulting from the knockdown of ASK1 modulates the migration of breast cancer cells.

• Authors: Kyung Tae Noh, Ssang-Goo Cho, Eui-Ju Choi
• Journal: FEBS letters (FEBS Lett) Vol. 584 Issue 18 Pg. 4097-101 (Sep 24 2010) ISSN: 1873-3468 [Electronic] England
• PMID: 20800594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• beta Catenin
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• MAP Kinase Kinase Kinase 5
• MAP3K5 protein, human
• Glycogen Synthase Kinase 3

Topics

• Apoptosis (genetics)
• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Gene Knockdown Techniques
• Glycogen Synthase Kinase 3 (antagonists & inhibitors, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• MAP Kinase Kinase Kinase 5 (genetics)
• beta Catenin (antagonists & inhibitors, metabolism)