期刊
CELL COMMUNICATION AND SIGNALING
卷 11, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1478-811X-11-51
关键词
Metastasis; Sarcoma; RhoA; ROCK; MLC; Amoeboid invasiveness; 3D environment; Chicken model
类别
资金
- Kellner Family Foundation
- Ministry of Education, Youth and Sports of the Czech Republic [MSM0021620858, LC06061]
- Academy of Sciences of the Czech Republic [RVO 68378050]
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. Conclusion: 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.
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