Inhibition of invasion by glycogen synthase kinase-3 beta inhibitors through dysregulation of actin re-organisation via down-regulation of WAVE2

Yuki Yoshino; Manami Suzuki; Hidekazu Takahashi; Chikashi Ishioka

doi:10.1016/j.bbrc.2015.06.142

Inhibition of invasion by glycogen synthase kinase-3 beta inhibitors through dysregulation of actin re-organisation via down-regulation of WAVE2

Biochem Biophys Res Commun. 2015 Aug 14;464(1):275-80. doi: 10.1016/j.bbrc.2015.06.142. Epub 2015 Jun 24.

Authors

Yuki Yoshino¹, Manami Suzuki¹, Hidekazu Takahashi¹, Chikashi Ishioka²

Affiliations

¹ Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
² Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan; Department of Medical Oncology, Tohoku University Hospital, Tohoku University, Seiryo-machi 1-1, Aoba-ku, Sendai 980-8574, Japan. Electronic address: [email protected].

PMID: 26116771
DOI: 10.1016/j.bbrc.2015.06.142

Abstract

Cancer cell invasion is a critical phenomenon in cancer pathogenesis. Glycogen synthase kinase-3β (GSK-3β) has been reported to regulate cancer cell invasion both negatively and positively. Thus, the net effect of GSK-3β on invasion is unclear. In this report, we showed that GSK-3β inhibitors induced dysregulation of the actin cytoskeleton and functional insufficiency of focal adhesion, which resulted in suppressed invasion. In addition, WAVE2, an essential molecule for actin fibre branching, was down-regulated after GSK-3β inhibition. Collectively, we propose that the WAVE2-actin cytoskeleton axis is an important target of GSK-3β inhibitors in cancer cell invasion.

Keywords: Actin cytoskeleton; Focal adhesion; GSK-3β; WAVE2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actin Cytoskeleton / drug effects*
Actin Cytoskeleton / enzymology
Actin Cytoskeleton / ultrastructure
Actins / chemistry
Actins / genetics
Actins / metabolism
Cell Adhesion / drug effects
Cell Line, Tumor
Cell Movement / drug effects*
Collagen / chemistry
Drug Combinations
Focal Adhesions / drug effects
Focal Adhesions / enzymology
Focal Adhesions / ultrastructure
Gene Expression
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / genetics
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Humans
Laminin / chemistry
Protein Kinase Inhibitors / pharmacology*
Proteoglycans / chemistry
Thiazoles / pharmacology*
Urea / analogs & derivatives*
Urea / pharmacology
Wiskott-Aldrich Syndrome Protein Family / antagonists & inhibitors*
Wiskott-Aldrich Syndrome Protein Family / genetics
Wiskott-Aldrich Syndrome Protein Family / metabolism

Substances

Actins
Drug Combinations
Laminin
Protein Kinase Inhibitors
Proteoglycans
Thiazoles
WASF2 protein, human
Wiskott-Aldrich Syndrome Protein Family
matrigel
N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea
Urea
Collagen
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3