title: Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell Biology, Faculty of Science, Charles University in Prague, Viničná 7, 12843 Prague 2, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kosla
authors.forename: Daniela
authors.initials: D
authors.lastname: Paňková
authors.forename: Jiří
authors.initials: J
authors.lastname: Plachý
authors.forename: Ondřej
authors.initials: O
authors.lastname: Tolde
authors.forename: Kristýna
authors.initials: K
authors.lastname: Bicanová
authors.forename: Michal
authors.initials: M
authors.lastname: Dvořák
authors.forename: Daniel
authors.initials: D
authors.lastname: Rösel
authors.forename: Jan
authors.initials: J
authors.lastname: Brábek
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002645:Chickens; D018994:Myosin Light Chains / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051381:Rats; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins
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