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

0423218 - ÚMG 2014 RIV GB eng J - Článek v odborném periodiku
Kosla, Jan - Paňková, D. - Plachý, Jiří - Tolde, O. - Bicanova, K. - Dvořák, Michal - Rosel, D. - Brabek, J.
Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling.
Cell communication and signaling : CCS. Roč. 11, č. 1 (2013), s. 51. E-ISSN 1478-811X
Grant CEP: GA MŠMT(CZ) LC06061
Institucionální podpora: RVO:68378050
Klíčová slova: metastasis * sarcoma * rhoA * ROCK * MLC * amoeboid invasiveness * 3D environment * chicken model
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.672, rok: 2013

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.
Trvalý link: http://hdl.handle.net/11104/0229368