糖原合酶激酶-3β抑制剂通过下调WAVE2导致肌动蛋白重组失调从而抑制侵袭。

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

作者信息

Yoshino Yuki, Suzuki Manami, Takahashi Hidekazu, Ishioka Chikashi

机构信息

Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.

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.

出版信息

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

DOI:10.1016/j.bbrc.2015.06.142

PMID:26116771

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.

摘要

癌细胞侵袭是癌症发病机制中的一个关键现象。据报道，糖原合酶激酶-3β（GSK-3β）对癌细胞侵袭具有正向和负向调节作用。因此，GSK-3β对侵袭的净效应尚不清楚。在本报告中，我们发现GSK-3β抑制剂会导致肌动蛋白细胞骨架失调和粘着斑功能不全，从而抑制侵袭。此外，肌动蛋白纤维分支的关键分子WAVE2在GSK-3β抑制后表达下调。我们共同提出，WAVE2-肌动蛋白细胞骨架轴是GSK-3β抑制剂在癌细胞侵袭中的重要靶点。