Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling

Cell Communication and Signaling

Research

Daniel Rösel¹  Jan Brábek¹  Daniela Paňková¹  Ondřej Tolde¹  Kristýna Bicanová¹  Michal Dvořák²  Jan Kosla²  Jiří Plachý² 

[1] Department of Cell Biology, Faculty of Science, Charles University in Prague, Viničná 7, 12843, Prague 2, Czech Republic;Laboratory of Molecular Virology or Cellular and Viral Genetics, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220, Prague 4, Czech Republic;

关键词: Metastasis;    Sarcoma;    RhoA;    ROCK;    MLC;    Amoeboid invasiveness;    3D environment;    Chicken model;   

DOI  :  10.1186/1478-811X-11-51

 received in 2013-04-15, accepted in 2013-07-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundAlthough there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process.ResultsWe analyzed the dependence of amoeboid invasiveness of rat and chicken sarcoma cells and the metastatic activity of chicken cells on individual elements of the Rho/ROCK/MLC pathway. In both animal models, inhibition of Rho, ROCK or MLC resulted in greatly decreased cell invasiveness in vitro, while inhibition of extracellular proteases using a broad spectrum inhibitor did not have a significant effect. The inhibition of both Rho activity and MLC phosphorylation by dominant negative mutants led to a decreased capability of chicken sarcoma cells to metastasize. Moreover, the overexpression of RhoA in non-metastatic chicken cells resulted in the rescue of both invasiveness and metastatic capability. Rho and ROCK, unlike MLC, appeared to be directly involved in the maintenance of the amoeboid phenotype, as their inhibition resulted in the amoeboid-mesenchymal transition in analyzed cell lines.ConclusionTaken together, these results suggest that protease-independent invasion controlled by elements of the Rho/ROCK/MLC pathway can be frequently exploited by metastatic sarcoma cells.

【 授权许可】

Unknown   
© Kosla et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.