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

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 (Gro alpha) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Gro alpha exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Gro alpha in HNSCC tissues; indicate that Gro alpha 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 Gro alpha in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Gro alpha 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 Gro alpha 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 Gro alpha, beta-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, sug-gesting that the EMT and metastasis processes were activated by Gro alpha. These findings constitute the first evi-dence that Gro alpha promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Gro alpha in mediating metastasis and its potential as a therapeutic target.

Automated summary

Squamous cell carcinoma (SCC) is a common malignant tumor in the head and neck region, often detected late with poor prognosis and survival rate. The growth-related oncogene alpha (Gro alpha) is highly expressed in SCC and associated with tumor metastasis and invasion. This study shows that Gro alpha promotes epithelial mesenchymal transition (EMT) and matrix metalloproteinase (MMP) expression in HNSCC through activation of CXCR1/2, suggesting that Gro alpha may play a role in mediating metastasis.