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Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation

Oncogene volume 34, pages 1141–1149 (2015)Cite this article

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Abstract

Dlg5 has been reported to participate in cancer progression; however, its role in prostate cancer still remains poorly understood. In this study, we demonstrate that Dlg5 is frequently downregulated in prostate cancer. We show here that Dlg5 is involved in the regulation of cell migration and cancer cell invasion. Knockdown of endogenous Dlg5 markedly increased prostate cancer cell migration and invasion. Our studies, for the first time, demonstrate the interaction between Dlg5 and Girdin, an actin-binding Akt substrate. Importantly, we found that levels of Akt-mediated Girdin phosphorylation (p-Girdin-Ser1416) are increased in Dlg5-depleted cells. Small interfering RNA directed against Girdin and wortmannin treatment, which was found to reduce Girdin phosphorylation, impaired the effect of Dlg5 depletion on cell migration. Taken together, our findings demonstrate that Dlg5 interacts with and inhibits the activity of Girdin, thereby suppressing the migration of prostate cancer cells.

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Acknowledgements

This work was supported in part by the Asahi Glass Foundation, a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and a grant from the Bio-oriented Technology Research Advancement Institution.

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Authors and Affiliations

  1. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

    L Tomiyama, T Sezaki, M Matsuo, K Ueda & N Kioka

  2. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan

    K Ueda

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  1. L Tomiyama
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  2. T Sezaki
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  3. M Matsuo
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  4. K Ueda
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  5. N Kioka
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Correspondence to N Kioka.

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Tomiyama, L., Sezaki, T., Matsuo, M. et al. Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation. Oncogene 34, 1141–1149 (2015). https://doi.org/10.1038/onc.2014.31

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  • DOI: https://doi.org/10.1038/onc.2014.31

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