Overexpression of Tiam1 promotes the progression of laryngeal squamous cell carcinoma

Abstract

Abstract. 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.

<p>High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis</p>

“…First, metastasis is an essential hall marker of cancer and always leads to poor survival. [41][42][43] Numerous studies suggested that Tiam1 contributed to invasion and metastasis in various cancers, including osteosarcoma, 44 retinoblastoma, 45 gastric cancer, 46 CRC, [47][48][49][50][51] hepatocellular carcinoma, 25,52 breast cancer, 53 cholangiocarcinoma, 54 cervical cancer, 20 ovarian cancer, 55 nasopharyngeal cancer, 8,16 laryngeal cancer, 56 thyroid carcinoma, 57 nom-small cell lung cancer, 48 pancreatic cancer 6,58,59 and oral squamous cell carcinoma 27 Malliri et al reported that Tiam1 could facilitate E-cadherin-based adhesions between cancer cells in mouse intestinal tumors and human colon tumors, resulting in invasion and metastasis 60 Epithelial-mesenchymal transition (EMT) is a key process of enhancing cancer cell migration, invasion and metastasis. [28][29][30][31] Liu et al reported that Tiam1 overexpression could promote invasiveness and metastasis of thyroid carcinoma in vitro and in vivo by activating Wnt/EMT pathway 57 Similarly, Ding 6 and Yang et al 20 that Tiam1 overexpression could also boost invasion and metastasis of pancreatic cancer and cervical cancer by inducing EMT.…”

<p>Up-Regulation of Tiam1 Promotes the Radioresistance of Laryngeal Squamous Cell Carcinoma Through Activation of the JNK/ATF-2 Signaling Pathway</p>

“…The TU686 cells that transfected with Tiam1/C1199 cDNA and vector control plasmid were named Tiam1+ and Mock, respectively, as established and described in our previous study. 24 …”

“…All Western blotting analyses were performed as we described previously. 24 Briefly, total protein (40 μg/sample) was separated in SDS-PAGE (8%) and then electroblotted onto polyvinylidene difluoride membranes (Immobilon-P, Millipore, USA). The membranes were separately incubated with anti-Tiam1 mouse monoclonal antibody (sc-393,315, dilution 1:100) (Santa Cruz, CA, USA), rabbit monoclonal antibody against JNK (ab179461, dilution 1:1000) and phosphate (p)-JNK (ab124956, dilution 1:1000) (Abcam, Cambridge, UK), mouse monoclonal antibody against ATF-2 (sc-242, dilution 1:200), and p-ATF-2 (sc-8398, dilution 1:100) (Santa Cruz, CA, USA) at 4°C overnight.…”

“…Our previous experiment results demonstrated that Tiam1 expression may correlate with the tumorigenesis and development of LSCC and may be a beneficial therapeutic target for LSCC patients. 24 Nevertheless, there are relatively few reports on the role of Tiam1 on LSCC radioresistance. In an attempt to gain further insight into the radioresistance of Tiam1 in LSCC and its probable mechanism, here we report that the transfection of a Tiam1/C1199 plasmid to up-regulate Tiam1 expression in LSCC, and we observed changes in the proliferation, apoptosis and the expression of JNK/ATF-2 signaling pathway both in vitro and in vivo after radiation.…”

Regulation of the retinoblastoma tumor suppressor by the novel Ras effector NORE1A.

“…It mediates a broad range of cellular processes, including cellular migration and adhesion (134). It has been reported that over-expression of TIAM1 is correlated with poor prognosis in patients with hepatocellular carcinoma (135), and additional reports have now shown that alterations in TIAM1 expression/function may contribute to tumorigenesis and carcinoma progression of common types of cancer (136)(137)(138)(139). Interestingly, TIAM1 preferentially associates with activated GTP-bound Ras through a Ras-binding domain; this was shown to promote the activation of Rac in a PI3K-independent manner (140).…”