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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 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) 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 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.

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.

Emerging evidence has demonstrated the altered expression of mRNAs in cancer development and progression. In this study, the precise role of miRNA-22 (miR-22) in colon cancer cells was investigated. Upon transfection with a miR-22 expression vector, the viability of HCT-116 human colon cancer cells was significantly reduced and tumor cell migration and invasion capacity were also suppressed. Computational in silico analysis predicted that T-cell lymphoma invasion and metastasis 1 (TIAM1) is a target gene of miR-22. This was confirmed by qRT-PCR and western blotting, which showed that miR-22 expression inhibited TIAM1 mRNA and protein expression, respectively. In addition, the expression of pro-invasive gene matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and pro-angiogenic protein vascular endothelial growth factor (VEGF) were also reduced by miR-22 expression. Collectively, these data suggest that miR-22 may act as a tumor suppressor in colon cancer, most likely by targeting TIAM1 expression.

Tiam1 has been implicated in the invasive phenotype of various carcinomas. However, its role in ovarian cancer remains to be elucidated, including its upstream regulatory mechanisms. In the present study, we examined the differential expression of Tiam1 in 10 normal ovarian tissues and 17 paired primary and corresponding metastatic ovarian cancer tissues by semi-quantitative immunohistochemistry. It was found that Tiam1 expression was remarkably increased in both primary and metastatic ovarian cancer tissues relative to normal ovarian tissues. Loss-of-function study revealed that downregulation of Tiam1 in SKOV-3ip and HO-8910PM cells lead to reduced cell migration and invasion, and growth inhibition without significantly affecting cell apoptosis. Subsequent regulatory study further confirmed the negative regulatory effects of miR-22, miR-183 and miR-31 on Tiam1 expression. Taken together, our data suggested that Tiam1 may be involved in the aggressive behavior of ovarian cancer, and differential expression profiles of microRNA (miRNA) may contribute to the dysregulation of Tiam1 abundance, which contributes to the invasive, migratory and viability properties of ovarian cancer cells.

Accumulating evidence has demonstrated that T-cell lymphoma invasion and metastasis 1 (Tiam1) plays an important role in the occurrence and development of several different tumors; however, to date, little research has been done to verify the potential role of Tiam1 as a prognostic marker for esophageal squamous cell carcinoma (ESCC). In the present study, we examined the expression of Tiam1 in ESCC tissues by immunohistochemistry, in situ hybridization, semi-quantitative RT-PCR and Western blotting methods and investigated the correlation between Tiam1 levels and prognosis of patients with ESCC. Tiam1 exhibited high expression in ESCC tissues, whereas the normal esophageal tissues showed negative or weak Tiam1 expression. Additionally, Tiam1 mRNA and protein expression levels were both significantly correlated with histology grade, clinical staging and lymph node metastasis (all P0.05), but not related to age and gender (both P0.05). Further, ESCC patients with strong Tiam1 mRNA (P=0.000) and protein (P=0.000) expression had a poorer prognosis than those with weak expression. These findings demonstrate that Tiam1 may be used as molecular marker for predicting the prognosis of patients with ESCC.

In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely related to the plasminogen activator inhibitor (PAI-1) and estrogen receptor (ER) expression but not the progesterone receptor (PR) and urokinase plasminogen activator (uPA). A low Tiam1 expression was associated with p53 positivity without being related to HER2/neu status. The data show that Tiam1 expression decreases with the progression of breast carcinomas and is inversely associated with several established breast tumor markers. Therefore, we suggest that Tiam1 counteracts the progression of breast carcinomas and is suitable as a novel breast tumor marker.

p27Kip1 is a cyclin-dependent kinase inhibitor which regulates progression of cells from G1 into S phase in a cell cycle. p27Kip1 has been reported to be an important prognostic factor in various malignancies. As the ability of invasion and metastasis has been thought to be the most important factor for patient's prognosis, we examined whether up-regulation or down-regulation of p27Kip1 can affect the ability of invasion and metastasis of an oral cancer cell (B88t cell) in vitro and in vivo. We constructed an expression vector containing sense- or antisense-oriented human p27Kip1 cDNA with pcDNA3.1. We transfected B88t cells with the empty vector, the sense- or antisense-oriented expression vector to regulate the expression of p27Kip1 gene. Up-regulation of p27Kip1 protein markedly inhibited the migration of cancer cells in a Boyden chamber. Down-regulation of p27Kip1 protein markedly enhanced the migration of cancer cells in a Boyden chamber, and the tumor invasion in nude mice. Moreover, we detected up-regulation of E-cadherin and down-regulation of Tiam-1 (tumor invasive and metastasis-1) in the sense transfectants, up-regulation of Tiam-1 and down-regulation of E-cadherin in the antisense transfectants by Western blotting. These results suggest that p27Kip1 may play an important role in the invasion and metastasis of an oral cancer cell involved in regulation of E-cadherin and Tiam-1.