title: 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.affiliation: Laboratories of Cell Death and Human Diseases, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D038362:Glycogen Synthase Kinase 3