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

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 li...

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Bibliographic Details
Published in:Oral oncology 2008-07, Vol.44 (7), p.683-688
Main Authors: Lai, Stephen Y, Ziober, Amy F, Lee, Megan N, Cohen, Noam A, Falls, Erica M, Ziober, Barry L
Format: Article
Language:English
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
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Summary: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.
ISSN:1368-8375
1879-0593
DOI:10.1016/j.oraloncology.2007.08.017