LIM-kinase is critical for the mesenchymal-to-amoeboid cell morphological transition in 3D matrices
LIM-kinase is critical for the mesenchymal-to-amoeboid cell morphological transition in 3D matrices
复制标题
DOI：
10.1016/j.bbrc.2010.01.075
复制
发表时间：
2010-02-19
影响因子：
3.1
通讯作者：
Mizuno, Kensaku
中科院分区：
文献类型：
--
作者：
Mishima, Toshiaki;Naotsuka, Moyu;Mizuno, Kensaku
肿瘤细胞可以在三维基质中以间质样或变形虫模式迁移。HT1080纤维肉瘤细胞在3D胶原凝胶中培养后，在蛋白酶抑制剂（PI）处理或激活Rho或ROCK表达后，其形态从间充质样（细长）变为变形虫样（圆形）。在这项研究中，我们研究了LIMK1在PI-或Rho/ rock诱导的细胞形态学改变中的作用。我们发现，HT1080细胞在3D胶原凝胶中经过PI处理后，LIMK1被激活，这种激活被ROCK抑制剂阻断。而LIMK1过表达诱导细胞圆整，敲低LIMK1或激酶失活的LIMK1表达抑制PI-或Rho/ rock诱导的细胞圆整。这些结果表明，LIMK1在3D胶原凝胶培养HT1080细胞的PI-或Rho/ rock诱导的间质细胞向变形虫细胞的形态转变中起重要作用。此外，LIMK1敲低可抑制HT1080细胞在含或不含pi的胶原凝胶中的侵袭活性，表明LIMK1介导HT1080细胞的间质和变形虫侵袭模式。(C) 2010爱思唯尔公司版权所有。
Tumor cells can migrate in 3D matrices in either a mesenchymal-like or amoeboid mode. HT1080 fibrosarcoma cells cultured in 3D collagen gels change their morphology from mesenchymal-like (elongated) to amoeboid (round) following protease inhibitor (PI) treatment or active Rho or ROCK expression. In this study, we examined the role of LIM-kinase 1 (LIMK1) in the PI- or Rho/ROCK-induced cell morphological change. We showed that LIMK1 was activated after PI treatment of HT1080 cells in 3D collagen gels and this activation was blocked by a ROCK inhibitor. While overexpression of LIMK1 induced cell rounding, knockdown of LIMK1 or the expression of kinase-inactive LIMK1 suppressed PI- or Rho/ROCK-induced cell rounding. These results suggest that LIMK1 plays an essential role in the PI- or Rho/ROCK-induced mesenchymal-to-amoeboid cell morphological transition of HT1080 cells cultured in 3D collagen gels. Furthermore, LIMK1 knockdown suppressed the invasive activity of HT1080 cells in collagen gels with or without PIs, indicating that LIMK1 mediates both the mesenchymal and amoeboid modes of invasion of HT1080 cells. (C) 2010 Elsevier Inc. All rights reserved.