Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions
Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions
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DOI：
10.1128/mcb.26.3.898-911.2006
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Kikuchi, A
中科院分区：
文献类型：
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作者：
Kobayashi, T;Hino, S;Kikuchi, A
H-Prune是一种糖原合成酶-3(GSK-3)结合蛋白，被认为与细胞迁移有关。用GSK-3抑制剂或针对GSK-3和h-prune的小干扰RNA(SiRNA)处理培养细胞，可抑制细胞的运动。GSK-3与h-prune的相互作用需要GSK-3的激酶活性。H-prune定位于局部粘连，GSK-3或h-prune的siRNA延迟了巴西林的解体。在GSK-3或h-prune基因敲除的细胞中，粘着斑激酶(FAK)的酪氨酸磷酸化和Rac的激活均受到抑制。GSK-3抑制剂可抑制巴西林的解离和FAK和Rac的激活。此外，h-prune在结直肠癌和胰腺癌中高表达，且h-prune的阳性表达与肿瘤的侵袭性有关。这些结果表明，GSK-3和h-prune协同调节局部粘连的解体以促进细胞迁移，h-prune可作为肿瘤侵袭性的标志。
h-prune, which has been suggested to be involved in cell migration, was identified as a glycogen synthase kinase 3 (GSK-3)-binding protein. Treatment of cultured cells with GSK-3 inhibitors or small interfering RNA (siRNA) for GSK-3 and h-prune inhibited their motility. The kinase activity of GSK-3 was required for the interaction of GSK-3 with h-prune. h-prune was localized to focal adhesions, and the siRNA for GSK-3 or h-prune delayed the disassembly of paxillin. The tyrosine phosphorylation of focal adhesion kinase (FAK) and the activation of Rac were suppressed in GSK-3 or h-prune knocked-down cells. GSK-3 inhibitors suppressed the disassembly of paxillin and the activation of FAK and Rac. Furthermore, h-prune was highly expressed in colorectal and pancreatic cancers, and the positivity of the h-prune expression was correlated with tumor invasion. These results suggest that GSK-3 and h-prune cooperatively regulate the disassembly of focal adhesions to promote cell migration and that h-prune is useful as a marker for tumor aggressiveness.