Growth regulated oncogene-α contribute to EMT/MMPs pathway by binding its receptors in head and neck squamous cell carcinoma

Abstract

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, β-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target.