Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma

• Published in: Oral oncology Vol. 44; no. 7; pp. 683 - 688
• Main Authors: Lai, Stephen Y, Ziober, Amy F, Lee, Megan N, Cohen, Noam A, Falls, Erica M, Ziober, Barry L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2008; Elsevier
• Subjects: Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cdc42; cdc42 GTP-Binding Protein - metabolism; Female; GTPase-Activating Proteins - metabolism; Guanine Nucleotide Exchange Factors - metabolism; Hematology, Oncology and Palliative Medicine; Humans; Invasion; Male; Medical sciences; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neoplasm Invasiveness; Oral squamous cell carcinoma; Otolaryngology; Otorhinolaryngology. Stomatology; Rac1; rac1 GTP-Binding Protein - metabolism; rhoA GTP-Binding Protein - metabolism; Signal Transduction; Tumor Cells, Cultured; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Vav2; OSCC; Immunoprecipitation; Guanine nucleotide exchange factors; IP; GEF; Oral squamous cell carcinoma; FACS; Invasion; Vav2; Guanine nucleotide binding protein; Immunoblot; Flow activated cytometry sorting; IB; Rac1; GTPase; Cdc42; Stomatology; Tumorous infiltration; ENT; Malignant tumor; Cancerology; Oral cavity disease; Cell; Cancer
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2007.08.017

Summary 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.