Epidermal growth factor receptor (EGFR) is overexpressed in
head and neck squamous cell carcinoma (
HNSCC) where it has been shown to promote
tumor cell invasion upon phosphorylation. One mechanism by which EGFR promotes
tumor progression is by activating signal cascades that lead to loss of
E-cadherin, a transmembrane
glycoprotein of the cell-cell adherence junctions; however mediators of these signaling cascades are not fully understood. One such mediator, RhoC, is activated upon a number of external stimuli, such as
epidermal growth factor (
EGF), but its role as a mediator of
EGF-stimulated migration and invasion has not been elucidated in
HNSCC. In the present study, we investigate the role of RhoC as a mediator of
EGF-stimulated migration and invasion in
HNSCC. We show that upon
EGF stimulation, EGFR and RhoC were strongly activated in
HNSCC. This resulted in activation of the
phosphatidylinositol 3-Kinase Akt pathway (PI3K-Akt), phosphorylation of GSK-3β at the Ser(9) residue, and subsequent down regulation of
E-cadherin cell surface expression resulting in increased
tumor cell invasion. Knockdown of RhoC restored
E-cadherin expression and inhibited
EGF-stimulated migration and invasion. This is the first report in
HNSCC demonstrating the role RhoC plays in mediating
EGF-stimulated migration and invasion by down-regulating the PI3K-Akt pathway and
E-cadherin expression. RhoC may serve as a treatment target for
HNSCC.