Research Article: High SRC-1 and Twist1 expression predicts poor prognosis and promotes migration and invasion by inducing epithelial-mesenchymal transition in human nasopharyngeal carcinoma

Date Published: April 11, 2019

Publisher: Public Library of Science

Author(s): Jingchun Zhou, Jingjing Zhang, Ming Xu, Zhaoyang Ke, Wei Zhang, Jiahao Mai, Jung Weon Lee.

http://doi.org/10.1371/journal.pone.0215299

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.

Partial Text

Nasopharyngeal carcinoma (NPC), a unique malignancy arising from the epithelium of nasopharynx, is characterized by its unique geographic distribution [1]. NPC has the highest incidence in southern China, Southeast Asia and North Africa, but it is rare in the rest part of the world [2]. According to global cancer statistics from the International Agency for Research on Cancer, nearly 80% new NPC cases in 2008 were in Asia and only 5% were in Europe. Several factors have been implicated in the development of NPC, including genetic susceptibility, Epstein-Barr virus (EBV) infection and chemical carcinogens [3–5]. Besides, NPC is a poorly or undifferentiated carcinoma. It has high radio- and chemosensitivity, and a great propensity for distant metastasis [6]. Thus, radiotherapy is recommended for the treatment of nonmetastatic disease and has a high cure rate for patients with low NPC stages. However, the majority of NPC patients are diagnosed with locally advanced stages. Various modes of combined chemoradiotherapy have been used to treat these NPC patients, but the 5-year overall survival rate were only 53%-80% and 28%-61% in NPC stages III and IV, respectively [7, 8]. To date, genomic abnormalities of NPC remain obscure and no targeted therapy has been established. Therefore, it is urgent to find molecular targets which can predict prognosis or guide for targeted therapy in NPC.

In the present study, 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. Moreover, we found that 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 EMT. Our data indicated that Src-1 and Twist1 could be important biomarkers to predict outcome and potential therapy targets for NPC patients.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving animals were in accordance with the ethical standards of the ethics committee of the Shenzhen People’s Hospital at which the studies were conducted.

 

Source:

http://doi.org/10.1371/journal.pone.0215299

 

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