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

Oncogene. 2010 Aug 19;29(33):4636-47. doi: 10.1038/onc.2010.216.

P U Le ¹, 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

Affiliations

Affiliation

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

PMID: 20543869 DOI: 10.1038/onc.2010.216

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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