Abstract
RAS oncogenes play a critical role in oncogenic transformation and metastases formation. Here we show that Ha-ras greatly stimulates spontaneous metastatic activity of transformed cells through the Ras/RalGDS/RalA intracellular signaling pathway. Introduction of RalA alone leads to a drastic increase of metastatic activity of transformed cells. We demonstrate that metastatic ability of cells could be dramatically enhanced by RalA stimulation or, conversely, hampered by RalA suppression. Furthermore, we found that during in vivo selection cells acquire high metastatic properties as a result of endogenous RalA activation. The ability of RalA to induce metastasis was demonstrated in spontaneously transformed as well as in virus transformed fibroblasts.
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Acknowledgements
We thank J Downward and H Koide for provision of Ha-Ras and RalA mutant containing vectors, A Tavitian, G Deichman, B Kopnin and O Mizenina for support and fruitful discussion and N Isachenko for technical assistance. This study was supported by the Russian National Foundation for Basic Research, Grant No. 02-04-48626.
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Tchevkina, E., Agapova, L., Dyakova, N. et al. The small G-protein RalA stimulates metastasis of transformed cells. Oncogene 24, 329–335 (2005). https://doi.org/10.1038/sj.onc.1208094
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DOI: https://doi.org/10.1038/sj.onc.1208094
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