Abstract
Incidence of kidney cancer is on the rise, and a better understanding of molecular mechanisms involved in the cancer invasion and metastasis is required for the development of curative therapeutics. In this study, we report that the proinflammatory cytokine prostaglandin E2 (PGE2) induces the malignant SN12C, but not benign HK2 kidney cell invasion. The PGE2 increases SN12C cell invasion through a signal pathway that encompasses EP2 and EP4, Akt, small GTPase RalA and Ral·GTP inactivator RGC2. The results support the idea that targeted interference of EP2/EP4 signal to RalA·GTP may provide benefit to patients diagnosed with advanced kidney cancer.
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Acknowledgements
We thank Dr A Saltiel for providing anti-RGC2 and anti-phospho-RGC2 antibodies and the NCI for providing the SN12C cancer cells. We also thank Ms E Grigson and Ms K Durst for editorial assistance, and Dr Z Nie for reading and commenting on the manuscript. This work was supported, in part, by US National Institutes of Health grant R01 CA129155 (to YD).
Author Contributions: ZL, YZ, WK and YD designed the experiments. ZL, YZ and WK performed all the experiments in this work. ZL and YD wrote the paper.
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Li, Z., Zhang, Y., Kim, W. et al. PGE2 promotes renal carcinoma cell invasion through activated RalA. Oncogene 32, 1408–1415 (2013). https://doi.org/10.1038/onc.2012.161
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DOI: https://doi.org/10.1038/onc.2012.161
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