Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma.
The Rho family of GTPases regulates cellular adhesion and motility. Guanine nucleotide exchange factors (GEFs) in turn regulate GTPases by promoting nucleotide exchange from GDP to GTP. We have determined that GTP-bound Rac1 is elevated in invasive oral squamous cell carcinoma (OSCC) cell lines. Because of the critical role of invasion in the progression and metastasis of OSCC, we investigated if the GEF Vav2 modulated Rac1 and Cdc42 activation and thus influenced OSCC invasion. Expression levels of Vav2 did not correlate with invasion but phosphorylated or activated Vav2 was associated with the more invasive cell lines. Transfection of activated Vav2 into the immortalized keratinocyte cell line HaCat and a low-level expressing Vav2 invasive OSCC cell line resulted in increased GTP-bound Rac1 and Cdc42 and increased invasion. Thus, activation of Vav2 appears to modulate cellular invasion through specific regulation of Rac1 and Cdc42 activity in OSCC.
Lai
Stephen Y
SY
Molecular Tumor Biology Laboratory, Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Health System, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Ziober
Amy F
AF
Lee
Megan N
MN
Cohen
Noam A
NA
Falls
Erica M
EM
Ziober
Barry L
BL
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein