TSPAN8 serves as a prognostic marker involving Akt/MAPK pathway in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common epithelial carcinoma with high occurrence and metastatic rates in Southern China. To date, the molecular mechanisms of metastasis for NPC remains unclear. The aim of this study was to discover the underlying mechanism of NPC and to elucidate novel genes that may play important roles in NPC progression and metastasis.

We carry out mRNA expression profiling, Arraystar Human mRNA Expression Profiling Service Report based on polymerase chain reaction (PCR) using four pairs of tumor tissues and their corresponding benign adjacent tissues from NPC patients.

We found that 1,787 genes were differentially expressed, among them, 8 genes were identified as highly upregulated in NPC patients. Within these 8 genes, only TSPAN8 was consistently over-expressed in poorly differentiated CNE2 cell line and highly-metastatic subclone S18 cell line. TSPAN8 mRNA and protein levels were increased in primary carcinoma tissues compared to their corresponding adjacent benign tissues. Knockdown of TSPAN8 by siRNA resulted in inhibition of NPC cell migration and invasion, while overexpression of TSPAN8 promoted NPC cell migration, invasion and proliferation. To explore the potential metastasis pathway mechanism for NPC, TSPAN8 were silenced in CNE2 cell. From the Tumor Metastasis Pathway Finder PCR array, knockdown of TSPAN8 led to the down-regulation of IL-1β, which showed the most down-regulation among identified genes. IL-1β is a regulating factor of the Akt/MAPK pathway, which is involved in the cancer cell migration regulation. Furthermore, the down-regulation of TSPAN8 in CNE2 cell was associated with inhibition of the Akt/MAPK pathway. Immunohistochemistry (IHC) indicated that TSPAN8 level was increased in NPC tumors, which was associated with shorter overall survival and metastasis free survival (MFS).

The data indicated that TSPAN8 acting as a tumor migration marker and may be a prognostic factor or therapeutic target for NPC.