Overexpression of Tiam1 is associated with malignant phenotypes of nasopharyngeal carcinoma

Ding,Yi; Chen,Bin; Huang,Jing; Zhang,Wenli; Yang,Hongjun; Deng,Yongjian; Lin,Jie; Wang,Shuang; Zhang,Xiangmei

doi:10.3892/or.2014.3241

Overexpression of Tiam1 is associated with malignant phenotypes of nasopharyngeal carcinoma

Authors:
- Yi Ding
- Bin Chen
- Jing Huang
- Wenli Zhang
- Hongjun Yang
- Yongjian Deng
- Jie Lin
- Shuang Wang
- Xiangmei Zhang
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Affiliations: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Academic Research and Medical Training, General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong 510515, P.R. China, Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: June 6, 2014 https://doi.org/10.3892/or.2014.3241
Pages: 607-618

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Abstract

The aim of the present study was to analyze the roles of T lymphoma invasion and metastasis 1 (Tiam1) in nasopharyngeal carcinoma (NPC) progression and its correlation with clinicopathological features, including the survival of patients with NPC. Tiam1 protein expression in NPC tissues was examined using immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were performed to detect the expression of Tiam1 in 6 NPC cell lines. Stable Tiam1-overexpressing NPC cells using a transfection technique and Tiam1-silencing NPC cells using short hairpin RNA were constructed. Subsequently, MTT assay, plate and soft agar colony formation assays, cell adhesion, migration, invasion assays and experimental animal models were carried out to detect the biological functions of Tiam1 in vitro and in vivo. Immunohistochemical analysis revealed that Tiam1 had high expression in 96 of 140 (68.6%) paraffin-embedded archival NPC biopsies. Tiam1 overexpression was significantly associated with N classification (P=0.004), distant metastasis (P=0.042) and clinical stage (P=0.042). Patients with higher levels of Tiam1 expression had poorer overall survival (P=0.002). Multivariate analysis revealed that Tiam1 expression is an independent prognostic indicator for the overall survival of NPC patients. Using the approaches of exogenous overexpression and the knockdown of Tiam1 expression, respectively, it was confirmed that Tiam1 promoted cell proliferation, adhesion, invasion and migration in vitro and in vivo. These data support the notion that Tiam1 plays an important role in the progression of NPC, and the overexpression of Tiam1 is associated with malignant phenotypes of NPC.

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