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

Kyung Tae Noh, Ssang Goo Cho, Eui Ju Choi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4097-4101
Number of pages5
JournalFEBS Letters
Volume584
Issue number18
DOIs
Publication statusPublished - 2010 Sept

Bibliographical note

Funding Information:
We would like to thank Dr. Woo Keun Song (GIST of South Korea) for the pTopflash plasmid. This work was supported by a NRF Grant (2010-0001197), by the Original Technology Research Program for Brain Science (2010-0002153) and the Mid-career Researcher Program (2010-0000488) through NRF Grant funded by the Ministry of Education, Science & Technology (MEST) of the Korea (E.-J.C.).

Keywords

  • ASK1
  • Axin
  • GSK-3β
  • Migration
  • β-Catenin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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