Research and Development-Process Development (O&O-PO), Nederlands Vaccin Instituut (NVI) , Bilthoven, The Netherlands.
Zebrafish. 2009 Dec;6(4):433-9. doi: 10.1089/zeb.2009.0602.
The two LIM kinases (LIMKs) LIMK1 and LIMK2 are members of the PDZ/LIM family. These serine/threonine protein kinases are involved in actin cytoskeleton reorganization through phosphorylation and inactivation of ADF/cofilin. Different subcellular localizations of LIMK1 and LIMK2 suggest different functions. LIMK1 is implicated in microtubule disassembly in endothelial- and cancer cells, whereas LIMK2 plays a role in cell cycle progression. To compare the role of the two LIMKs in cancer-related processes, we used a cell-based in vitro migration assay, as well as two zebrafish xenograft assays. We analyzed here the metastatic behavior and tumor cell-induced neovascularization of pancreatic cancer cells in which both LIMK genes were silenced by siRNAs. Both LIMK1 and LIMK2 single knock down led to a reduction of invasion and metastatic behavior in the zebrafish xenograft metastasis assay. Interestingly, the double knock down completely blocked invasion and formation of micrometastasis in vivo. Moreover, in the zebrafish xenograft angiogenesis assay, we observed a reduction of pancreatic cancer cell-induced angiogenesis for both the LIMK1 and LIMK2 knockdowns. Our results demonstrate similar functions for the two LIMKs in pancreatic cancer cells and suggest an important role for both LIMK1 and LIMK2 in tumor progression and metastasis formation.
两种 LIM 激酶(LIMKs)LIMK1 和 LIMK2 是 PDZ/LIM 家族的成员。这些丝氨酸/苏氨酸蛋白激酶通过磷酸化和失活 ADF/cofilin 参与肌动蛋白细胞骨架重组。LIMK1 和 LIMK2 的不同亚细胞定位表明其具有不同的功能。LIMK1 参与内皮细胞和癌细胞中的微管解体,而 LIMK2 在细胞周期进程中发挥作用。为了比较两种 LIMK 在与癌症相关的过程中的作用,我们使用了基于细胞的体外迁移测定法,以及两种斑马鱼异种移植测定法。在这里,我们分析了沉默两种 LIMK 基因的 siRNA 后胰腺癌细胞的转移行为和肿瘤细胞诱导的血管生成。LIMK1 和 LIMK2 的单独敲低均导致斑马鱼异种移植转移测定中侵袭和转移行为的减少。有趣的是,双重敲低完全阻止了体内侵袭和微转移的形成。此外,在斑马鱼异种移植血管生成测定中,我们观察到两种 LIMK1 和 LIMK2 敲低均导致胰腺癌细胞诱导的血管生成减少。我们的结果表明,两种 LIMK 在胰腺癌细胞中具有相似的功能,并表明 LIMK1 和 LIMK2 在肿瘤进展和转移形成中均具有重要作用。
Int J Biochem Cell Biol. 2007
Gene Expr Patterns. 2007-4
Cells. 2021-12-28
Bioessays. 2025-1
Cancers (Basel). 2023-10-19
Cells. 2021-12-15
Wiley Interdiscip Rev Dev Biol. 2021-11