Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
- Equal contributors
1 Department of Cell Biology, Faculty of Science, Charles University in Prague, Viničná 7, 12843, Prague 2, Czech Republic
2 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
Cell Communication and Signaling 2013, 11:51 doi:10.1186/1478-811X-11-51Published: 30 July 2013
Although 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.
We 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.
Taken 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.