GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) – a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1.19 using western blot analysis and real-time PCR. Inhibition of the RhoA/ROCK signaling pathway by the pharmacological inhibitor fasudil reduced vascular-like channels of U2OS cells in Matrigel. Furthermore, we used rhodamine–phalloidin immunofluorescence, wound healing assay, and transwell migration assay to examine the effect of fasudil on tumor cell plasticity and motility, both of which play key roles in VM formation. Finally, we explored the underlying mechanisms of fasudil-induced VM destruction. In this context, we showed that the RhoA/ROCK signaling pathway is a novel regulator in VM of U2OS OS cells and suggest that fasudil in conjunction with established treatments may present a novel therapeutic strategy for OS.
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Publication date: Available online 18 January 2017 Source: Free Radical Biology and Medicine Author(s): Jayne Louise Wilson, Frédéric Boui...
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Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
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Publication date: July 2017 Source: European Journal of Cancer, Volume 79 Author(s): Simon Pernot, Cecile Badoual, Magali Terme, Florence...
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Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compou...
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An ambitious plan to save a melting glacier in the Swiss Alps with showers of artificial snow will be tested this summer from #AlexandrosS...
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by Yiquan Wu, Adrian Prager, Simone Boos, Moritz Resch, Ilija Brizic, Michael Mach, Sabrina Wildner, Laura Scrivano, Barbara Adler Herpesv...
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A mass-change-based method based on output-only data for the rescaling of mode shapes in operational modal analysis (OMA) is introduced. The...
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In this study, the changes in pH, organic acid content, acidity, and salinity of kimchi prepared at 0 days, stored 1–8 weeks at 4 and 10°C, ...
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