Tiam1 Transgenic Mice Display Increased Tumor Invasive and Metastatic Potential of Colorectal Cancer after 1,2-Dimethylhydrazine Treatment

Yu, Lei; Zhang, Qingling; Li, Xin; Hua, Xin; Cui, Yejia; Zhang, Nian-Jie; Liao, Wenting; Ding, Yan‐Qing

doi:10.1371/journal.pone.0073077

Cited by 18 publications

(14 citation statements)

References 27 publications

(35 reference statements)

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“…However, a significant decrease in tumor growth was observed with olive oil treatment. Our results are supported by reports published in the literature which demonstrated that DMH treatment enhanced tumor incidence, tumor multiplicity and tumor growth . However, Sánchez‐Fidalgo et al .…”

Section: Discussionsupporting

confidence: 91%

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Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Nanda

Mahmood

Bhatia

et al. 2018

Intl Journal of Cancer

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Epigenetic therapy induced by dietary components has become a strong interest in the field of cancer prevention. Olive oil, a potent dietary chemopreventive agent, control colon cancer, however, its role in epigenetic therapy remains unclear. Thus, we aimed to investigate the effect of olive oil in a preclinical model of colon cancer by targeting genetic and epigenetic mechanisms. DMH was used to induce colon cancer in rats; while olive oil was given to separate group of rats along with DMH treatment. Tumor burden and incidence in DMH and DMH + olive oil-treated rats was observed by macroscopic examination and histoarchitectural studies. Potent anti-inflammatory, anti-angiogenic and pro-apoptotic activity of olive oil was explored by gene expression and immunohistochemical studies. The effect of olive oil on epigenetic alterations was examined by detecting promoter methylation with MS-HRM and dysregulation of miRNA by TaqMan MicroRNA Assay. We observed that olive oil administration lowered tumor incidence and inhibited the development of tumors in DMH-treated rats. Olive oil markedly decreased the expression of inflammatory and angiogenic markers and restored the expression of pro-apoptotic markers in DMH-treated rats. Furthermore, the inverse relationship between gene expression and DNA methylation, deviant miRNA pattern and miRNA silencing mediated by aberrant DNA methylation was also seen in DMH-treated rats, which was potentially reversible upon olive oil treatment. Our study concludes that olive oil may play a role in the epigenetic therapy by altering NF-κB and apoptotic pathways via targeting noncoding RNAs and methylation machinery that affecting epigenome to prevent colon carcinogenesis.

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Section: Discussionsupporting

confidence: 91%

“…The results were confirmed by histoarchitectural studies that showed a clear demonstration of inhibition of tumor growth by administration of olive oil. Based on the results of H&E staining of the colonic tissues, it is well documented that administration of DMH in vivo promotes colon carcinogenesis . However, Sánchez‐Fidalgo et al .…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Nanda

Mahmood

Bhatia

et al. 2018

Intl Journal of Cancer

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“…19 One in vivo study found that TIAM1 promotes invasion and metastasis of colorectal cancer, possibly through activation of the Wnt/betacatenin signaling pathway in a TIAM1 transgenic mouse model. 20 In line with our observation, it has also been shown that suppression of TIAM1 is required for enhanced cell migration and invasion in human colorectal cancer enteroid models. 21 Our findings also show significant down-regulation of AMOTL1 in colon cancer tissues compared with normal mucosa.…”

Section: Discussionsupporting

confidence: 89%

Differential Expression of Tight Junctions and Cell Polarity Genes in Human Colon Cancer

Kourkoumpetis¹,

Royse²,

Chen³

et al. 2018

Exploratory Research and Hypothesis in Medicine

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Background and objectives: Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls. Methods:Total RNA was extracted from fresh frozen tumor tissues and normal adjacent tissues of 6 patients who were diagnosed with primary colon cancer as well as from normal mucosa of 5 unrelated polyp-free individuals. We used the Qiagen RT 2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student's t-test was used to compare gene expression levels between cancer tissues and normal mucosa using normalized gene expression data. Results:Compared with normal mucosa, significant up-regulation of the claudin 1 (CLDN1) gene (fold-change = 16, p = 0.001) but down-regulation of the AMOTL1, CLDN5, JAM2 and TIAM1 genes (fold-change > 2, p < 0.05) were seen in colon cancer tissue. Conclusions:We observed the differential expression of CLDN, AMOTL1, JAM2 and TIAM1 in colon cancer versus normal mucosa. Further larger studies are warranted to investigate the role of tight junction and cell polarity proteins in the progression of human colon tumors.

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“…Yu et al demonstrated that Tiam1 was upregulated in colorectal carcinoma tissues and provided evidence that Tiam1 was closely correlated to the metastatic potential of colorectal carcinoma. Depletion of Tiam1 significantly reduced the tumor growth and metastatic ability of colorectal carcinoma cells (26). However, its role in ovarian carcinoma remains to be elucidated.…”

Section: A B a Bmentioning

confidence: 98%

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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Tiam1 Transgenic Mice Display Increased Tumor Invasive and Metastatic Potential of Colorectal Cancer after 1,2-Dimethylhydrazine Treatment

Cited by 18 publications

References 27 publications

Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Chemopreventive role of olive oil in colon carcinogenesis by targeting noncoding RNAs and methylation machinery

Differential Expression of Tight Junctions and Cell Polarity Genes in Human Colon Cancer

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

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