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Overexpression of Tiam 1 promotes the progression of laryngeal squamous cell carcinoma

T-lymphoma invasion and metastasis-inducing factor 1 (Tiam1) has been reported in various types of human cancer, which play important roles in facilitating the metastasis of malignant tumor. However, the investigation of Tiam1 in laryngeal squamous-cell carcinoma is extremely rare. The aim of the present study was to assess Tiam1 expression and examine its function in tumorigenesis and the metastasis of laryngeal squamous cell carcinoma (LSCC) in vitro. Tiam1 expression in 98 primary LSCC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' survival. To investigate the effects of Tiam1 on the progression of LSCC, Tiam1/C1199 plasmid was transfected into LSCC, and proliferation, apoptosis, migration and invasion of transfected cells were examined using MTT, flow cytometry, wound-healing and Transwell assay, respectively. The results showed that, Tiam1 was detected in all primary LSCC samples. Additionally, Tiam1 overexpression was closely correlated with tumor progression and patient survival. Tiam1 overexpression was statistically significant, and served as an independent predictor of prognosis for patients with LSCC. The upregulation of Tiam1 by Tiam1/C1199 plasmid had no effect on the proliferation of transfected cells, but decreased the apoptotic rate of transfected cells, while the ability of migration and invasion was increased. These results suggested that Tiam1 overexpression in LSCC is possibly involved in the promotion of migration and invasion, and is a promising therapeutic target in the prevention of the progression of LSCC. Introduction Laryngeal squamous cell carcinoma (LSCC) is a common tumor occurring in the head and neck, and accounts for ~5% of all cancer cases (1). Despite advances in the development of conventional therapies such as surgery, radiotherapy and chemotherapy, the 5-year survival rate for patients with LSCC remains unsatisfactory (~50-70%) (2). Locoregional recurrences, lymph node and distant metastasis are major causes of death that significantly affect prognosis in LSCC patients (3). Therefore, the recognition and identification of tumor markers associated with recurrence and/or metastasis is of great value in the prediction of malignant biological behavior and the direction of therapeutic strategies. T-lymphoma invasion and metastasis-inducing factor 1 (Tiam1), as an invasion and metastasis-inducing gene, was first identified by proviral tagging in combination with in vitro selection for invasiveness from a murine T-lymphoma cell line (4). The Rho-like small guanosine triphosphate (GTP)-binding proteins, as molecular switches, cycle between an inactive and an active GTP-bound state. Guanine nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP, positively stimulte these GTP-binding proteins in response to various signaling pathways (5). Tiam1, as a member of Db1 family proteins, is a specific GEF for the Rho-like GTP-binding protein Rac, which is involved in cell migration, invasion and metastasis (6). Tiam1 overexpression is prevalent in numerous solid tumors, including those of prostate (7), hepatocellular (8,9), nasopharyngeal (10), esophageal (11) and renal cell carcinoma (12), colorectal cancer (13) and gallbladder carcinoma (14). Tiam1 is also reported to have intimate correlations with apoptosis (15), invasion and migration (16,17). Therefore, the overexpression of Tiam1 is important in the progression of malignant tumors. However, to the best of our knowledge, few studies evaluating the role of Tiam1 protein expression in LSCC are available. Consequently, we investigated Tiam1 expression in a number of LSCC tissue samples and assessed whether Tiam1 expression was correlated with clinicopathological parameters and prognosis in LSCC patients. Moreover, Tiam1/C1199 plasmid was employed to upregulate Tiam1 expression in LSCC cell lines, and the roles of Tiam1 in LSCC cell growth, apoptosis, migration, and invasion in vitro were investigated. Overexpression of Tiam1 promotes the progression of laryngeal squamous cell carcinoma SHuANG WANG*, SHiSHENG Li*, QiNGLAi TANG, SHu YANG, SHuHui WANG, JiAJiA Liu, Mi YANG and XiNMiNG YANG Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South university, Changsha, Hunan 410011, P.R. China Received December 3, 2014; Accepted January 21, 2015 DOi: 10.3892/or.2015.3785 Correspondence to: Dr Xinming Yang, Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South university, 139 Renmin Road, Changsha, Hunan 410011,