Role of synaptojanin 2 in glioma cell migration and invasion.
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.
Chuang
Ya-Yu
YY
Center for Oncology and Cell Biology, Institute for Medical Research at North Shore-LIJ, Manhasset, New York 11030, USA.
Tran
Nhan L
NL
Rusk
Nicole
N
Nakada
Mitsutoshi
M
Berens
Michael E
ME
Symons
Marc
M
D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D051381:Rats
D017931:DNA Primers; D009419:Nerve Tissue Proteins; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases