CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma

Du, Chunping; Huang, Tingting; Sun, Di; Mo, Yuchang; Feng, Hao; Zhou, Xiaoying; Xiao, Xue; Yu, Nana; Hou, Bo; Ernberg, Ingemar; Zhang, Zhe

doi:10.1016/j.canlet.2011.05.016

Cited by 46 publications

(36 citation statements)

References 26 publications

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“…This gene encodes for the R-cadherin protein, which is expressed in various tissues with a wide range of functionality. In the brain, R-cadherin plays a role in establishing axonal guidance; while in other tissue, R-cadherin is involved in cell-cell cohesion, inhibition of apoptosis and cell signaling, and tumorigenesis (Du et al, 2011). Therefore, our results show that the generation of this CNA in vitro could be a potential genetic mechanism behind alterations in observed mRNA expression, although more studies are needed for further assessment.…”

Section: Discussionmentioning

confidence: 99%

Atrazine exposure elicits copy number alterations in the zebrafish genome

Wirbisky

Freeman

2017

Comparative Biochemistry and Physiology Part C: Toxicology &

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Atrazine is an agricultural herbicide used throughout the Midwestern United States that frequently contaminates potable water supplies resulting in human exposure. Using the zebrafish model system, an embryonic atrazine exposure was previously reported to decrease spawning rates with an increase in progesterone and ovarian follicular atresia in adult females. In addition, alterations in genes associated with distinct molecular pathways of the endocrine system were observed in brain and gonad tissue of the adult females and males. Current hypotheses for mechanistic changes in the developmental origins of health and disease include genetic (e.g., copy number alterations) or epigenetic (e.g., DNA methylation) mechanisms. As such, in the current study we investigated whether an atrazine exposure would generate copy number alterations (CNAs) in the zebrafish genome. A zebrafish fibroblast cell line was used to limit detection to CNAs caused by the chemical exposure. First, cells were exposed to a range of atrazine concentrations and a crystal violet assay was completed, showing confluency decreased by ∼60% at 46.3 μM. Cells were then exposed to 0, 0.463, 4.63, or 46.3 μM atrazine and array comparative genomic hybridization completed. Results showed 34, 21, and 44 CNAs in the 0.463, 4.63, and 46.3μM treatments, respectively. Furthermore, CNAs were associated with previously reported gene expression alterations in adult male and female zebrafish. This study demonstrates that atrazine exposure can generate CNAs that are linked to gene expression alterations observed in adult zebrafish exposed to atrazine during embryogenesis providing a mechanism of the developmental origins of atrazine endocrine disruption.

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Section: Discussionmentioning

confidence: 99%

Atrazine exposure elicits copy number alterations in the zebrafish genome

Wirbisky

Freeman

2017

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…In some cancers, for example, leiomyoma and ovarian carcinoma, CDH4 was treated as proto-oncogene, CDH4 gene expression was upregulated [18]. However, in some other cancers, such as nasopharyngeal carcinoma, gastric cancer, and colorectal cancer, CDH4 acted as anti-oncogene, CDH4 gene expression was downregulated[11, 12]. In lung cancer, our study suggested that CDH4 might serve as tumor surpressor gene, though more research need to be conducted.…”

Section: Discussionmentioning

confidence: 99%

Study on expression of CDH4 in lung cancer

Li¹,

Su²,

Liu³

et al. 2017

World J Surg Onc

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BackgroundThe human CDH4 gene, which encodes the R-cadherin protein, has an important role in cell migration and cell adhesion, sorting, tissue morphogenesis, and tumor genesis. This study analyzed the relationship of CDH4 mRNA expression with lung cancer.MethodsReal time PCR was applied to detect CDH4 mRNA transcription in 142 paired cases of lung cancer and noncancerous regions.ResultsNo correlation was identified between CDH4 mRNA expression and gender, age, lymphnode metastasis, TNM stage, family history, smoking state, drinking state (P > 0.05), but grade and histotype (P < 0.05). The relative CDH4 mRNA value was remarkably decreased in lung cancer tissues compared with noncancerous tissues (P = 0.001).ConclusionsWe found that CDH4 mRNA expression was associated with grade and histotype. What is more, the relative CDH4 mRNA value was decreased in the lung cancer tissues. Our results suggested that CDH4 might be a putative tumor suppressor gene (TSG) in lung cancer.

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“…In 2008, Kucharczak [37] found that the overexpression of R-cadherin in myoblast cell can affect its endogenous N-cadherin and M-cadherin function then inhibit myogenesis and induce myoblast transformation via Rac1 GTPase. In recent years, aberrant promoter methylation of CDH4 was detected in both gastrointestinal tumor and nasopharyngeal carcinoma, respectively [38–40], which demonstrated CDH4 methylation may be a common phenomenon in the process of tumorigenesis. CDH4 was also considered as a potential tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

Efficient isolation and proteomic analysis of cell plasma membrane proteins in gastric cancer reveal a novel differentiation and progression related cell surface marker, R-cadherin

et al. 2016

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Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin positive expression displayed better overall survivals than negative expression group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed lacking the expression of R-cadherin was a main independent predictor for poor clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250–14.341, P < 0.01). We have established a fundamental membrane proteome database for gastric cancer and identified R-cadherin as a tumor differentiation and progression-related cell surface marker of gastric cancer. Lacking the expression of R-cadherin indicates poor prognosis in patients with gastric cancer.

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CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma

Cited by 46 publications

References 26 publications

Atrazine exposure elicits copy number alterations in the zebrafish genome

Atrazine exposure elicits copy number alterations in the zebrafish genome

Study on expression of CDH4 in lung cancer

Efficient isolation and proteomic analysis of cell plasma membrane proteins in gastric cancer reveal a novel differentiation and progression related cell surface marker, R-cadherin

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