title: RhoC mediates epidermal growth factor-stimulated migration and invasion in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: From the College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854 USA.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Tumur
authors.affiliation: From the College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854 USA.
authors.forename: Shahbaz
authors.initials: S
authors.lastname: Katebzadeh
authors.affiliation: From the College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854 USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Guerra
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854 USA.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Bhushan
authors.affiliation: College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854 USA.
authors.forename: Tursun
authors.initials: T
authors.lastname: Alkam
authors.affiliation: From the College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854 USA. Electronic address: bhenson@westernu.edu.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Henson
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics*; D000075024:rhoC GTP-Binding Protein
chemical_list: D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein