<i>NDRG4</i> is Downregulated in Glioblastoma and Inhibits Cell Proliferation

Ding, Wenchao; Zhang, Jing; Yoon, Jae-Geun; Shi, Dongyan; Foltz, Gregory; Lin, Biaoyang

doi:10.1089/omi.2011.0146

Cited by 27 publications

(17 citation statements)

References 18 publications

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“…Previously, NDRG4 was mainly investigated in central nerve system tumors before. 6,23 However, in contrast, the present study together with our previous work in colorectal cancer indicated that NDRG4 expression level was decreased in gastrointestinal malignancy and had similar association with clinicopathological characteristics and prognosis. 24 In order to understand cellular function and mechanism of NDRG4 in gastric cancer, we carried out the in vitro experiment based on overexpression and knockdown of NDRG4 in gastric cancer cells.…”

Section: Discussioncontrasting

confidence: 73%

NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

Zhang

She

Yang

et al. 2018

Molecular Carcinogenesis

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As a novel candidate tumor suppressor, NDRG4 is largely unstudied in human malignancies. In this study, we investigated the protein expression level of NDRG4 in gastric cancer and its association with outcome of patients. In the present study, we recruited 286 patients with gastric cancer and investigated the protein and mRNA expression of NDRG4 in cancer and adjacent normal specimens by immunohistochemistry assay and real-time PCR. The association of NDRG4 level with clinicopathological characteristics was investigated by appropriate statistical analysis. NDRG4 overexpression and knockdown cell lines were established in order to detect its impact on proliferation and apoptosis. Significant decreased protein and mRNA expression of NDRG4 was found in gastric cancer, compared with adjacent normal specimens. Besides, it was found that NDRG4 protein expression in gastric cancer was significantly associated with tumor differentiation, invasion, metastasis, and stage. Patients with tumors of decreased NDRG4 level were more likely to have unfavorable disease-free and overall survival, in both univariate and multivariate analysis. In addition, overexpression of NDRG4 suppressed cell proliferation of gastric cancer cells in vitro; conversely, the proliferation of gastric cancer cells were enhanced by knockdown of NDRG4. These results proved for the first time that NDRG4 could be a potential tumor suppressor and prognostic marker of gastric cancer.

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Section: Discussioncontrasting

confidence: 73%

NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

Zhang

She

Yang

et al. 2018

Molecular Carcinogenesis

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“…In contrast to NDRG2, the studies regarding expression of NDRG4 in glioma show conflicting outcomes. One study described increased NDRG4 expression, while others report downregulation of NDRG4 in glioma [87][88][89][90]. Ding et al observed significantly decreased NDRG4 protein and mRNA expression in glioma tissue (n = 49) compared with normal tissue (n = 10), which was also confirmed using The Cancer Genome Atlas (TCGA; n = 410) data [87], and by Kolodziej et al [89].…”

Section: Gliomamentioning

confidence: 80%

“…One study described increased NDRG4 expression, while others report downregulation of NDRG4 in glioma [87][88][89][90]. Ding et al observed significantly decreased NDRG4 protein and mRNA expression in glioma tissue (n = 49) compared with normal tissue (n = 10), which was also confirmed using The Cancer Genome Atlas (TCGA; n = 410) data [87], and by Kolodziej et al [89]. In addition, reduced NDRG4 protein expression was found as a predictor for poor prognosis and reduced overall survival in both low-and high-grade gliomas (n = 128) [90].…”

Section: Gliomamentioning

confidence: 99%

Nervous NDRGs: the N-myc downstream–regulated gene family in the central and peripheral nervous system

et al. 2019

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The N-Myc downstream-regulated gene (NDRG) family consists of four members (NDRG1, NDRG2, NDRG3, NDRG4) that are differentially expressed in various organs and function in important processes, like cell proliferation and differentiation. In the last couple of decades, interest in this family has risen due to its connection with several disorders of the nervous system including Charcot-Marie-Tooth disease and dementia, as well as nervous system cancers. By combining a literature review with in silico data analysis of publicly available datasets, such as the Mouse Brain Atlas, BrainSpan, the Genotype-Tissue Expression (GTEx) project, and Gene Expression Omnibus (GEO) datasets, this review summarizes the expression and functions of the NDRG family in the healthy and diseased nervous system. We here show that the NDRGs have a differential, relatively cell typespecific, expression pattern in the nervous system. Even though NDRGs share functionalities, like a role in vesicle trafficking, stress response, and neurite outgrowth, other functionalities seem to be unique to a specific member, e.g., the role of NDRG1 in myelination. Furthermore, mutations, phosphorylation, or changes in expression of NDRGs are related to nervous system diseases, including peripheral neuropathy and different forms of dementia. Moreover, NDRG1, NDRG2, and NDRG4 are all involved in cancers of the nervous system, such as glioma, neuroblastoma, or meningioma. All in all, our review elucidates that although the NDRGs belong to the same gene family and share some functional features, they should be considered unique in their expression patterns and functional importance for nervous system development and neuronal diseases.

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“…N-Myc downstream-regulated gene (NDRG4), has been shown to bind the CDT of POPDC1. NDRG4 is a candidate tumor suppressor that is known to modulate cell migration, invasion, proliferation and angiogenesis [95][96][97]. The POPDC1-NDRG4 interaction was further shown to be essential in regulating the directional migration of epicardial cells [95].…”

Section: The Roles Of Popdc Proteins In Cell Migration Invasion and mentioning

confidence: 99%

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Amunjela

Swan

Brand

2019

Cells

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The Popeye domain containing (POPDC) gene family consists of POPDC1 (also known as BVES), POPDC2 and POPDC3 and encodes a novel class of cyclic adenosine monophosphate (cAMP) effector proteins. Despite first reports of their isolation and initial characterization at the protein level dating back 20 years, only recently major advances in defining their biological functions and disease association have been made. Loss-of-function experiments in mice and zebrafish established an important role in skeletal muscle regeneration, heart rhythm control and stress signaling. Patients suffering from muscular dystrophy and atrioventricular block were found to carry missense and nonsense mutations in either of the three POPDC genes, which suggests an important function in the control of striated muscle homeostasis. However, POPDC genes are also expressed in a number of epithelial cells and function as tumor suppressor genes involved in the control of epithelial structure, tight junction formation and signaling. Suppression of POPDC genes enhances tumor cell proliferation, migration, invasion and metastasis in a variety of human cancers, thus promoting a malignant phenotype. Moreover, downregulation of POPDC1 and POPDC3 expression in different cancer types has been associated with poor prognosis. However, high POPDC3 expression has also been correlated to poor clinical prognosis in head and neck squamous cell carcinoma, suggesting that POPDC3 potentially plays different roles in the progression of different types of cancer. Interestingly, a gain of POPDC1 function in tumor cells inhibits cell proliferation, migration and invasion thereby reducing malignancy. Furthermore, POPDC proteins have been implicated in the control of cell cycle genes and epidermal growth factor and Wnt signaling. Work in tumor cell lines suggest that cyclic nucleotide binding may also be important in epithelial cells. Thus, POPDC proteins have a prominent role in tissue homeostasis and cellular signaling in both epithelia and striated muscle.

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NDRG4 is Downregulated in Glioblastoma and Inhibits Cell Proliferation

Cited by 27 publications

References 18 publications

NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

Nervous NDRGs: the N-myc downstream–regulated gene family in the central and peripheral nervous system

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

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