Kobayashi Tsuyoshi, Hino Shin-ichiro, Oue Naohide, Asahara Toshimasa, Zollo Massimo, Yasui Wataru, Kikuchi Akira
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Mol Cell Biol. 2006 Feb;26(3):898-911. doi: 10.1128/MCB.26.3.898-911.2006.
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.
h-prune被认为参与细胞迁移，它被鉴定为糖原合酶激酶3（GSK-3）结合蛋白。用GSK-3抑制剂或针对GSK-3和h-prune的小干扰RNA（siRNA）处理培养细胞会抑制其运动性。GSK-3的激酶活性是GSK-3与h-prune相互作用所必需的。h-prune定位于粘着斑，针对GSK-3或h-prune的siRNA会延迟桩蛋白的解离。在GSK-3或h-prune敲低的细胞中，粘着斑激酶（FAK）的酪氨酸磷酸化和Rac的激活受到抑制。GSK-3抑制剂抑制了桩蛋白的解离以及FAK和Rac的激活。此外，h-prune在结直肠癌和胰腺癌中高表达，h-prune表达的阳性与肿瘤侵袭相关。这些结果表明，GSK-3和h-prune协同调节粘着斑的解离以促进细胞迁移，并且h-prune可作为肿瘤侵袭性的标志物。
