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GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring

Oncogene volume 28, pages 1339–1347 (2009)Cite this article

Abstract

GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motility by cytoskeletal remodeling, especially the formation of podosomes and. Here, we show that GRIM-19 inhibited the v-Src-induced cell motility by inhibiting cytoskeletal remodeling, that is, podosome formation. We also show that the N terminus of GRIM-19 played a major role in this process and identified critical residues in this region. More importantly, we show that tumor-associated GRIM-19 mutations disrupted its ability to inhibit v-Src-induced cell motility. These actions appear to occur independently of STAT3, a known target of GRIM-19-mediated inhibition. Lastly, tumor-associated GRIM-19 mutants significantly lost their ability to control v-Src-induced metastases in vivo, indicating the biological and pathological significance of these observations.

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Acknowledgements

DVK thanks National Cancer Institute (CA105005) for the grant support.

Author information

Author notes

  1. P Sun and S C Nallar: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    P Sun, S C Nallar, S Kalakonda & D V Kalvakolanu

  2. Molecular and Cellular Cancer Biology Graduate Track, The Graduate Program in Life Sciences, University of Maryland, Baltimore, MD, USA

    P Sun & D V Kalvakolanu

  3. Taussig Cancer Center and Department of Cancer Biology,

    D J Lindner

  4. The Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA

    D J Lindner

  5. Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    P Sun, S C Nallar, S Kalakonda, S S Martin & D V Kalvakolanu

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  1. P Sun
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  2. S C Nallar
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  3. S Kalakonda
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  4. D J Lindner
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  6. D V Kalvakolanu
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Correspondence to D V Kalvakolanu.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Sun, P., Nallar, S., Kalakonda, S. et al. GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring. Oncogene 28, 1339–1347 (2009). https://doi.org/10.1038/onc.2008.480

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