Abstract
T-lymphoma invasion and metastasis‑inducing factor1 (Tiam1) has been reported in various types of human cancer, which play important roles in facilitating the meta-stasis 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) invitro. 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 prolife-ration 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.
Highlights
Laryngeal squamous cell carcinoma (LSCC) is a common tumor occurring in the head and neck, and accounts for ~5% of all cancer cases [1]
T-lymphoma invasion and metastasis‐inducing factor 1 (Tiam1), as a member of Db1 family proteins, is a specific Guanine nucleotide exchange factors (GEFs) for the Rho-like guanosine triphosphate (GTP)‐binding protein Rac, which is involved in cell migration, invasion and metastasis [6]
And C, upregulated Tiam1 expression can lead to significantly increased migration (Hep-2/Tiam1 group, migration distance 147.00±26.06 vs. Hep-2, Hep-2/Mock control groups, migration distance 83.33±23.18 and 96.33±16.01; P=0.028) and invasion (68.33±6.66 vs. 43.00±8.89 and 45.00±7.55; P=0.013) of Hep-2 cells. These results clearly demonstrate that Tiam1 plays a functional role in mediating cell migration and invasion in LSCC, which are the key factors of LSCC malignant progression and metastasis
Summary
Laryngeal squamous cell carcinoma (LSCC) is a common tumor occurring in the head and neck, and accounts for ~5% of all cancer cases [1]. Locoregional recurrences, lymph node and distant metastasis are major causes of death that significantly affect prognosis in LSCC patients [3]. 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]. 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]
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