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DRR drives brain cancer invasion by regulating cytoskeletal-focal adhesion dynamics

Oncogene volume 29, pages 4636–4647 (2010)Cite this article

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Abstract

Malignant glioma invasion is a primary cause of brain cancer treatment failure, yet the molecular mechanisms underlying its regulation remain elusive. We developed a novel functional-screening strategy and identified downregulated in renal cell carcinoma (DRR) as a regulator of invasion. We show that DRR drives invasion in vitro and in vivo. We found that while DRR is not expressed in normal glial cells, it is highly expressed in the invasive component of gliomas. Exploring underlying mechanisms, we show that DRR associates with and organizes the actin and microtubular cytoskeletons and that these associations are essential for focal adhesion (FA) disassembly and cell invasion. These findings identify DRR as a new cytoskeletal crosslinker that regulates FA dynamics and cell movement.

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Acknowledgements

We are grateful to Carmen Sabau for her technical expertise. This work was supported by Goals for Lily, the Alex Pavanel Family, the Franco Di Giovanni Funds for Brain Tumor Research, the Montreal English School Board, the B-Strong Foundation to RFDM, and the Montreal Neurological Institute to KP. RMWO was supported by the Canadian Institute of Health Research doctoral fellowship. AAL was supported by the National Cancer Institute of Canada Terry Fox Studentship.

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  1. Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada

    P U Le, A Angers-Loustau, R M W de Oliveira, A Ajlan, C L Brassard, A Dudley, H Brent, V Siu, G Trinh, G Mölenkamp, J Wang, M Seyed Sadr, B Bedell, R F Del Maestro & K Petrecca

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  1. P U Le
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  2. A Angers-Loustau
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Correspondence to K Petrecca.

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Le, P., Angers-Loustau, A., de Oliveira, R. et al. DRR drives brain cancer invasion by regulating cytoskeletal-focal adhesion dynamics. Oncogene 29, 4636–4647 (2010). https://doi.org/10.1038/onc.2010.216

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