P1-3-5 - Angiotensin II Type 1 Receptor Signaling Promotes Head and Neck Cancer Cells Invasive Behavior by Flj10540/Mcp-1 Pathway

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the tumors of poor prognosis despite the therapeutic advances in the past few years. It has been reported that overexpression of AT1R occurs in many human carcinomas. However, the molecular mechanisms by which angiotensin II type 1 receptor (AT1R) mediate its invasive effects in HNSCC still unclear. Here, we found that AT1R was not only found in HNSCC specimens, but also significantly correlated with advanced TNM-stage and the poor 5-year survival rate. Thus indicated that AT1R was an independent factor for HNSCC development. Functionally, AT1R could promote tumor growth in nude mice. In addition, AT1R had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FLJ10540 and MCP-1 expression by Transwell chambers. Conversely, depletion of AT1R expression by siRNAs suppressed FLJ10540 and MCP-1 protein expressions. Suppression MCP-1 could cause significant inhibition on cell migratory and invasive ability of AT1R-overexpressing head and neck cancer cells. Finally, immunohistochemical and Western blotting analysis of human aggressive HNSCC specimens showed a significant positively correlation among AT1R, FLJ10540 and MCP-1 expression. These findings suggest that AT1R is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/MCP-1 pathway for HNSCC treatment.