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LIMK1 和 LIMK2 对于胰腺癌转移行为和肿瘤细胞诱导的血管生成很重要。

LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells.

机构信息

Research and Development-Process Development (O&O-PO), Nederlands Vaccin Instituut (NVI) , Bilthoven, The Netherlands.

出版信息

Zebrafish. 2009 Dec;6(4):433-9. doi: 10.1089/zeb.2009.0602.


DOI:10.1089/zeb.2009.0602
PMID:20047470
Abstract

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.

摘要

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。

相似文献

[1]
LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced angiogenesis of pancreatic cancer cells.

Zebrafish. 2009-12

[2]
LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators.

Med Res Rev. 2011-1-16

[3]
Lim kinases, regulators of actin dynamics.

Int J Biochem Cell Biol. 2007

[4]
LIMK2-1, a new isoform of human LIMK2, regulates actin cytoskeleton remodeling via a different signaling pathway than that of its two homologs, LIMK2a and LIMK2b.

Biochem J. 2018-12-6

[5]
LIM-kinase 2, a regulator of actin dynamics, is involved in mitotic spindle integrity and sensitivity to microtubule-destabilizing drugs.

Oncogene. 2009-11-2

[6]
Comparative analysis of splice form-specific expression of LIM Kinases during zebrafish development.

Gene Expr Patterns. 2007-4

[7]
The Role of LIM Kinase in the Male Urogenital System.

Cells. 2021-12-28

[8]
DADS downregulates the Rac1-ROCK1/PAK1-LIMK1-ADF/cofilin signaling pathway, inhibiting cell migration and invasion.

Oncol Rep. 2012-12-6

[9]
LIM Kinases, LIMK1 and LIMK2, Are Crucial Node Actors of the Cell Fate: Molecular to Pathological Features.

Cells. 2023-3-4

[10]
Different activity regulation and subcellular localization of LIMK1 and LIMK2 during cell cycle transition.

Exp Cell Res. 2006-4-15

引用本文的文献

[1]
Regulation and signaling of the LIM domain kinases.

Bioessays. 2025-1

[2]
PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development.

Cancers (Basel). 2023-10-19

[3]
LIMK2 promotes melanoma tumor growth and metastasis through G3BP1-ESM1 pathway-mediated apoptosis inhibition.

Oncogene. 2023-5

[4]
Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.

J Med Chem. 2022-10-27

[5]
LIMK1 Interacts with STK25 to Regulate EMT and Promote the Proliferation and Metastasis of Colorectal Cancer.

J Oncol. 2022-2-28

[6]
LIM Kinases in Osteosarcoma Development.

Cells. 2021-12-15

[7]
Upregulation of LIMK1 Is Correlated With Poor Prognosis and Immune Infiltrates in Lung Adenocarcinoma.

Front Genet. 2021-6-3

[8]
Unsupervised subtyping and methylation landscape of pancreatic ductal adenocarcinoma.

Heliyon. 2021-1-18

[9]
Zebrafish models of acute leukemias: Current models and future directions.

Wiley Interdiscip Rev Dev Biol. 2021-11

[10]
Phosphorylation-dependent regulation of SPOP by LIMK2 promotes castration-resistant prostate cancer.

Br J Cancer. 2021-3

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