Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion.
Members of the Rho family of small GTPases have been shown to be involved in tumorigenesis and metastasis. Currently, most of the available information on the function of Rho proteins in malignant transformation is based on the use of dominant-negative mutants of these GTPases. The specificity of these dominant-negative mutants is limited however. In this study, we used small interfering RNA directed against either Rac1 or Rac3 to reduce their expression specifically. In line with observations using dominant-negative Rac1 in other cell types, we show that RNA interference-mediated depletion of Rac1 strongly inhibits lamellipodia formation, cell migration and invasion in SNB19 glioblastoma cells. Surprisingly however, Rac1 depletion has a much smaller inhibitory effect on SNB19 cell proliferation and survival. Interestingly, whereas depletion of Rac3 strongly inhibits SNB19 cell invasion, it does not affect lamellipodia formation and has only minor effects on cell migration and proliferation. Similar results were obtained in BT549 breast carcinoma cells. Thus, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells.
Chan
Amanda Y
AY
Institute for Medical Research at North Shore-LIJ, Manhasset, NY 11030, USA.
Coniglio
Salvatore J
SJ
Chuang
Ya-yu
YY
Michaelson
David
D
Knaus
Ulla G
UG
Philips
Mark R
MR
Symons
Marc
M
D001932:Brain Neoplasms / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011554:Pseudopodia / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein
C411563:RAC3 protein, human; D034741:RNA, Small Interfering; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein