IQGAP1 promotes cell motility and invasion.
The dynamic processes of cell migration and invasion are largely coordinated by Rho family GTPases. The scaffolding protein IQGAP1 binds to Cdc42, increasing the amount of active Cdc42 both in vitro and in cells. Here we show that overexpression of IQGAP1 in mammalian cells enhances cell migration in a Cdc42- and Rac1-dependent manner. Importantly, cell motility was significantly decreased both by knock down of endogenous IQGAP1 using small interfering RNA and by transfection of a dominant negative IQGAP1 construct, IQGAP1DeltaGRD. Cell invasion was similarly altered by manipulating intracellular IQGAP1 concentrations. Moreover, invasion mediated by constitutively active Cdc42 was attenuated by IQGAP1DeltaGRD. Thus, IQGAP1 has a fundamental role in cell motility and invasion.
Mataraza
Jennifer M
JM
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts 02115, USA.
Briggs
Michael W
MW
Li
Zhigang
Z
Entwistle
Alan
A
Ridley
Anne J
AJ
Sacks
David B
DB
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005799:Genes, Dominant; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D010957:Plasmids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins; D005982:Glutathione Transferase; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein