Prognostic Value of Tiam1 and Rac1 Overexpression in Nasopharyngeal Carcinoma

Yan, Qi; Huang, Bo; Yu, Lan; Wang, Qi; Lan, Guiping; Zhang, Qiuhang

doi:10.1159/000223440

Cited by 33 publications

(30 citation statements)

References 34 publications

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“…Tiam1 maintains the specificity of rac1 toward specific downstream effector pathways, whereas rac1 regulates cell survival and cell-cycle progression (7,8). Together, Tiam1-rac1 is a critical component in the biology of human tumors, in both transformed cells as and the cells in the tumor microenvironment (9)(10)(11). Tiam1 is a potent modifier of oncogenic Ras-induced skin tumor initiation, promotion, and progression.…”

Section: Introductionmentioning

confidence: 99%

Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells

Guo

Wang

Jiang

et al. 2013

Molecular Cancer Research

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Tiam1 is a rac1-specific guanine nucleotide exchange factor, and Tiam1-rac1 is involved in a number of cellular processes. Rac1 and RhoA act as molecular switches that cycle between GTP-and GDP-bound states to balance the activities of rac1 and RhoA. The downregulation of rac1 activity leads to upregulation of RhoA activity, which promotes invasion and migration of pancreatic cancers cells. At present, however, the role of Tiam1-rac1 and RhoA in pancreatic cancers is not fully understood. We found that Tiam1 was upregulated in pancreatic cancers and was significantly expressed in tumors without lymph node involvement or distant metastasis compared with cancers where there was involvement. Although Tiam1-rac1 signaling promoted pancreatic cancer cell proliferation and tumor growth via the Wnt signaling pathway in vitro and in vivo, inhibiting Tiam1-rac1 signaling did not prolong the overall survival time in vivo. This provided evidence that there was a balance between rac1 and RhoA activities in pancreatic cancers. Furthermore, only the combined inhibition of Tiam1-rac1 and RhoA had a beneficial effect on the growth of pancreatic cancers in vivo. Taken together, these results suggest that the progression of pancreatic tumors is partially controlled by the balance between Tiam1-rac1 and RhoA.

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Section: Introductionmentioning

confidence: 99%

Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells

Guo

Wang

Jiang

et al. 2013

Molecular Cancer Research

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“…Yang et al recently reported that overexpression of Tiam1 was significantly correlated with vascular invasion status (P=0.02), intrahepatic metastasis status (P=0.009) and histological differentiation (P=0.008) of patients with hepatocellular carcinoma (15). In addition, Tiam1 was overexpressed in nasopharyngeal carcinoma cells and their protein up-regulation was significantly associated with stage and grading (P<0.05 for all) (12). Strong Tiam1 overexpression in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P=0.016), the presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (27).…”

Section: Disscussionmentioning

confidence: 94%

“…Increasing evidence has focused on the regulation of Tiam1 expression, as well as the role of Tiam1 in cancer progression and metastasis that Tiam1 specifically activates Rho-like GTPases (e.g., Rac1) and Tiam1-Rac1 pathway affects the migration and invasion of many tumors, such as nasopharyngeal carcinoma (12), breast cancer (13), retinoblastoma (14) and hepatocellular carcinoma (15). Additionally, overexpression of Tiam1 in tumor cells, implying a poor prognosis, has been linked to multiple different tumors (12)(13)(14)(15). However, to date, few studies have been performed to investigate whether Tiam1 plays a major role in the occurrence and development of ESCC and whether its overexpression implies poor prognosis of the patients with ESCC.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Tiam1 predicts poor prognosis in patients with esophageal squamous cell carcinoma

Liu

Shi²,

Liu³

et al. 2011

Oncol Rep

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Abstract. Accumulating evidence has demonstrated that Tcell 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 P<0.05), but not related to age and gender (both P>0.05). 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.

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“…Tiam1 maintains the specificity of Rac1 toward specific downstream effector pathways, whereas Rac1 regulates cell survival and cell cycle progression (8,9). Together, Tiam1-Rac1 is a critical component in the biology of human tumors, affecting the transformed cells themselves and the tumor microenvironment (10)(11)(12). Tiam1 is a potent modifier of oncogenic Ras-induced skin tumor initiation, promotion and progression (13).…”

Section: Introductionmentioning

confidence: 99%

“…Tiam1 is a potent modifier of oncogenic Ras-induced skin tumor initiation, promotion and progression (13). Moreover, numerous studies have demonstrated that the upregulation of Tiam1 is associated with an aggressive phenotype and a poor clinical outcome in several types of malignant tumors, including breast (14), colon (15), prostate (16), liver (17) and nasopharyngeal (11) esophageal squamous cell carcinoma (18). However, to date, the correlation between Tiam1 expression and ovarian carcinoma has not been adequately investigated.…”

Section: Introductionmentioning

confidence: 99%

Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma

Cui

Chen

et al. 2016

Oncology Letters

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Abstract. T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion-and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ 2 test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In conclusion, Tiam1 expression is strongly associated with grade and outcome in ovarian carcinoma, and may serve as a useful molecular marker for clinical management.

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Prognostic Value of Tiam1 and Rac1 Overexpression in Nasopharyngeal Carcinoma

Cited by 33 publications

References 34 publications

Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells

Balanced Tiam1-Rac1 and RhoA Drives Proliferation and Invasion of Pancreatic Cancer Cells

Overexpression of Tiam1 predicts poor prognosis in patients with esophageal squamous cell carcinoma

Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma

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