title: Inhibition of invasion by glycogen synthase kinase-3 beta inhibitors through dysregulation of actin re-organisation via down-regulation of WAVE2.
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.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: 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: chikashi@idac.tohoku.ac.jp.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007797:Laminin / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011509:Proteoglycans / Q000737:chemistry; D013844:Thiazoles / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D004338:Drug Combinations; D007797:Laminin; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; D013844:Thiazoles; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C059485:matrigel; C479831:N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea; D014508:Urea; D003094:Collagen; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Actin cytoskeleton; Focal adhesion; GSK-3β; WAVE2