RhoC mediates epidermal growth factor-stimulated migration and invasion in head and neck squamous cell carcinoma
| Autor: | Shahbaz Katebzadeh, Zohra Tumur, Tursun Alkam, Lokesh Bhushan, Bradley S. Henson, Carlos Guerra |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
rho GTP-Binding Proteins
Cancer Research STAT3 signal transducer and activator of transcription 3 RhoC Gene Expression epithelial cadherin E-cadherin Phosphatidylinositol 3-Kinases Epidermal growth factor Cell Movement Epidermal growth factor receptor Phosphorylation PI3K phosphatidylinositol 3-kinase lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cadherins Cell biology ErbB Receptors Head and Neck Neoplasms rhoC GTP-Binding Protein Gene Knockdown Techniques Carcinoma Squamous Cell Signal transduction RhoC GTP-Binding Protein Signal Transduction GSK3β glycogen synthase kinase 3 beta HNSCC head a neck squamous cell carcinoma Biology EMT epithelial mesenchymal transition ERK extracellular-signal-regulated kinase lcsh:RC254-282 Models Biological Article Cell Line Tumor medicine Humans HOK human oral keratinocytes Neoplasm Invasiveness PI3K/AKT/mTOR pathway EGF epidermal growth factor Epidermal Growth Factor Squamous Cell Carcinoma of Head and Neck medicine.disease Head and neck squamous-cell carcinoma EGFR epidermal growth factor receptor Tumor progression biology.protein Cancer research Snail Family Transcription Factors Proto-Oncogene Proteins c-akt MAPK mitogen-activated protein kinase Transcription Factors |
| Zdroj: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 17, Iss 1, Pp 141-151 (2015) |
| ISSN: | 1476-5586 |
| Popis: | 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 Ser9 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. |
| Databáze: | OpenAIRE |
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