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Role of Synaptojanin 2 in Glioma Cell Migration and Invasion

¹ Center for Oncology and Cell Biology, Institute for Medical Research at North Shore-LIJ, Manhasset, New York; ² Department of Surgery;, North Shore University Hospital, Manhasset, New York; ³ Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York; and ⁴ Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, Arizona

The small GTPase Rac1 is thought to play an important role in cell migration and invasion. We have previously identified synaptojanin 2, a phosphoinositide phosphatase, as an effector of Rac1. Here, we show that small interfering RNA-mediated depletion of either Rac1 or synaptojanin 2 inhibits invasion of SNB19 and U87MG glioblastoma cells through Matrigel and rat brain slices. Depletion of Rac1 or synaptojanin 2 also inhibits migration of SNB19 and U87MG cells on glioma-derived extracellular matrix. In addition, we found that depletion of Rac1 or synaptojanin 2 inhibits the formation of lamellipodia and invadopodia, specialized membrane structures that are thought to be involved in extracellular matrix degradation. These results suggest that synaptojanin 2 contributes to the role of Rac1 in cell invasion and migration by regulating the formation of invadopodia and lamellipodia. This study also identifies synaptojanin 2 as a novel potential target for therapeutic intervention in malignant tumors.

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