Abstract
Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC.
Highlights
Nasopharyngeal carcinoma (NPC), a unique malignancy arising from the epithelium of nasopharynx, is characterized by its unique geographic distribution [1]
We checked the protein expression of Steroid receptor coactivator 1 (Src-1) and Twist1 expression in several NPC cell lines, and found that Src-1 and Twist1 were high expressed in CNE-1 and low expressed in HNE-2 (Fig 1E)
We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and upregulation of Src-1 or Twist1 was associated with advanced tumor stage, distant metastasis and unfavorable prognosis
Summary
Nasopharyngeal carcinoma (NPC), a unique malignancy arising from the epithelium of nasopharynx, is characterized by its unique geographic distribution [1]. NPC is a poorly or undifferentiated carcinoma. It has high radio- and chemosensitivity, and a great propensity for distant metastasis [6]. Radiotherapy is recommended for the treatment of nonmetastatic disease and has a high cure rate for patients with low NPC stages. The majority of NPC patients are diagnosed with locally advanced stages. Genomic abnormalities of NPC remain obscure and no targeted therapy has been established.
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