DOC-2/DAB2 interactive protein regulates proliferation and mobility of nasopharyngeal carcinoma cells by targeting PI3K/Akt pathway.

Tumor suppressors are a group of important inverse regulators for carcinogenesis in human cancers including nasopharyngeal carcinoma (NPC). DOC-2/DAB2 interactive protein (DAB2IP) has been found to be a novel tumor suppressor in malignancies. However, the expression and biological function of DAB2IP in NPC have not been previously reported. This study found that the levels of DAB2IP were decreased in NPC tissues compared to non-cancerous nasopharyngeal epithelium tissues. In addition, downregulation of DAB2IP mRNA was confirmed by qRT-PCR in NPC cell lines as compared with a human immortalized nasopharyngeal epithelial cell line NP69. The reduced expression of DAB2IP was significantly correlated with lymph node metastasis and advanced clinical stage. DAB2IP low expressing NPC patients showed a notable reduced overall survival and disease-free survival. Functionally, DAB2IP restoration prohibited cell proliferation, colony formation, migration and invasion in both 5-8F and CNE-2 cells. Moreover, DAB2IP overexpression restrained the subcutaneous growth and lung metastasis of NPC cells in nude mice. Mechanically, DAB2IP overexpression repressed the activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and subsequently reduced the expression of its downstream targets including cyclin D1 and matrix metallopeptidase 7 (MMP7), which were identified as critical regulators for growth and metastasis of NPC. The Akt inhibitor MK-2206 showed similar effects to DAB2IP overexpression on growth and metastasis of 5-8F cells. Thus, DAB2IP suppresses growth and metastasis of NPC probably by targeting PI3K/Akt pathway, and may act as a hopeful therapeutic target for NPC.