Upregulation of Caveolin-1 correlate with Akt expression and poor prognosis in NPC patients.

Abstract

The aim of this study is to investigate the role of Caveolin-1 (Cav-1) in nasopharyngeal carcinoma (NPC) progression and correlated with clinical outcomes. We used quantitative real-time PCR (qPCR) to detect the difference in the expression of mRNA level of Cav-1 mRNA in NPC, non-NPC cell lines, and 74 NPC and 29 nontumorous nasopharyngeal mucosa biopsies. Western blotting and immunohistochemistry staining were used to detect the protein expression of Cav-1 in cell lines and biopsy tissues. We collected clinical follow-up data to investigate the association with expression of Cav-1 mRNA. Also, transfection of Cav-1 and suppression by delivery of shRNA against Cav-1 into NPC derived cell lines to analyze its influence in Akt signaling. By use of qPCR, immunohistochemical staining, and western blotting, we found that not only is Cav-1 overexpressed in human NPC tumor cells and NPC-derived cell lines but high Cav-1 mRNA expression is associated with poor overall survival time of NPC patients. Furthermore, phosphorylated Akt expression was enhanced by Cav-1 transfection and suppressed by delivery of shRNA against Cav-1. These data suggested a possible regulatory mechanism of Cav-1 on Akt signaling pathway. We also transfected the Cav-1 construct and shRNA in TW01 cells to prove the effect on Akt protein expression. Overexpression of Cav-1 is related to poor prognosis in NPC patients, which correlated with Akt signaling pathway. Abrogation of Akt signaling by shRNA-mediated knockdown of Cav-1 decreased malignant properties of tumor cells. These data suggest the potential for Cav-1 as a possible novel therapeutic target in NPC treatment.