Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Zhang, Zhiguo; Li, Gang; Feng, Dayun; Zhang, Jian; Zhang, Jing; Qin, Huaizhou; Ma, Liang; Gao, Guodong; Wu, Lin

doi:10.7314/apjcp.2014.15.1.239

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…To determine the functional role of NDRG2 in neuroblastoma, overexpression of NDRG2 was induced in the neuroblastoma cell lines SK-N-SH and SH-SY5Y, which resulted in an increased expression of the tumor suppressor gene protocadherin 17 and differentiation-related genes such as Rsu1 and Smurf1, and the decreased expression of proliferation-related genes such as CYR61. NDRG2 overexpression could thereby reduce cell proliferation compared with control cells [73].…”

Section: Neuroblastomamentioning

confidence: 97%

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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Section: Neuroblastomamentioning

confidence: 97%

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

et al. 2019

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“…The associations between NDRG2 and cancer have been reported in neurologic tumors [ 19 , 51 – 57 ], gastrointestinal tumors [ 9 – 11 , 13 , 14 , 55 , 58 – 75 ], genitourinary tumors [ 12 , 76 – 82 ], breast cancer [ 21 , 83 – 85 ], lung cancer [ 15 , 86 ], thyroid cancer [ 83 , 87 ], fibrosarcoma [ 88 ], oral squamous-cell carcinoma [ 89 ], myeloid leukemia [ 90 ] and cervical cancer (Hela cells) [ 25 ] (Table 1 ). Collectively, NDRG2 expression is associated with the clinical features of tumors.…”

Section: Associations Between Ndrg2 and Cancermentioning

confidence: 99%

Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer

Fan

Jiang

et al. 2015

Oncotarget

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N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor and cell stress-related gene. NDRG2 is associated with tumor incidence, progression, and metastasis. NDRG2 regulates tumor-associated genes and is regulated by multiple conditions, treatments, and protein/RNA entities, including hyperthermia, trichostatin A and 5-aza-2′-deoxycytidine, which are promising potential cancer therapeutics. In this review, we discuss the expression as well as the clinical and pathological significance of NDRG2 in cancer. The pathological processes and molecular pathways regulated by NDRG2 are also summarized. Moreover, mechanisms for increasing NDRG2 expression in tumors and the potential directions of future NDRG2 research are discussed. The information reviewed here should assist in experimental design and increase the potential of NDRG2 as a therapeutic target for cancer.

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“…Accumulating studies have shown that NDRG2 is associated with various nervous system diseases, including tumors, ischemic stroke, hemorrhage, trauma, and neurodegenerative disorders [1,59]. NDRG2 was repeatedly reported to be downregulated in a variety of cerebral tumors, including glioma and meningioma [21,[60][61][62][63][64][65][66]. The transcription levels of human NDRG2 are significantly reduced in human glioblastoma tissues and human glioblastoma cell lines, and exogenous overexpression of NDRG2 repressed glioblastoma cell proliferation in vitro [2].…”

Section: Ndrg2 In Brain Tumors and Other Nervous System Diseasesmentioning

confidence: 99%

N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Novel Tumor Suppressor in Multiple Human Cancers

Zhang¹,

Li²,

Shen³

et al. 2019

Genes and Cancer

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N-myc downstream-regulated gene 2 (NDRG2) was identified as a novel tumor suppressor gene in regulating the proliferation, differentiation, apoptosis and metastasis of multiple cancer types. Consistent with this finding, we and other groups observed the decreased NDRG2 expression in multiple human cancer cell lines and tumors, including breast cancer, colorectal cancer, and cervical cancer. We identified NDRG2 as a stress sensor for hypoxia, DNA damage stimuli and endoplasmic reticulum stress (ERS). Our recent data showed that NDRG2 could promote the differentiation of colorectal cancer cells. Interestingly, we found that reduced NDRG2 expression was a powerful and independent predictor of poor prognosis of colorectal cancer patients. Furthermore, NDRG2 can inhibit epithelial-mesenchymal transition (EMT) by positively regulating E-cadherin expression. Moreover, NDRG2-deficient mice show spontaneous development of various tumor types, including T-cell lymphomas, providing in vivo evidence that NDRG2 functions as a tumor suppressor gene. We believe that NDRG2 is a novel tumor suppressor and might be a therapeutic target for cancer treatment.Genes and Cancer 2 carcinoma cells [8]. Moreover, NDRG2-deficient mice show spontaneous development of various tumor types, providing in vivo evidence that NDRG2 functions as a tumor suppressor gene. In this chapter, we will introduce the recent findings of NDRG2 as tumor suppressor in vitro and in vivo, and also the detailed mechanism. NDRG2 as a hypoxia and DNA damage responderOur group firstly identified NDRG2 as a protein containing an acyl-carrier protein (ACP)-like domain. The gene was cloned from differentially expressed genes between glioblastoma and normal brain tissues using PCR-based subtractive hybridization in 2003. NDRG2, NDRG1, NDRG3, and NDRG4 comprise the NDRG gene family [1] and share approximately 59-68% homology. Additionally, NDRG family members display over 92% homology between humans and mice.The expression and cellular localization of NDRG2 were altered following exposure to different stresses, supporting the role of NDRG2 as a cellular stress sensor. Wang et al. found that NDRG2 expression was markedly upregulated in several cancer cell lines exposed to hypoxic conditions or similar stresses at both the mRNA and protein levels [9]. Hypoxia-inducible factor-1α (HIF-1α) can directly bind to hypoxia response elements (HREs) in the NDRG2 promoter, thus upregulating NDRG2 expression under hypoxia. Importantly, enforcing the expression of NDRG2 can strongly increase the apoptosis of cancer cells. Alternatively, NDRG2 can translocate from the cytoplasm to the nucleus under DNA damage stress. However, no explicit nuclear localization signal (NLS) sequence has been identified in the NDRG2 protein. Although NLSs are the most common type of nuclear import elements, other mechanisms may also be involved in NDRG2 translocation. For example, Liu et al. and Cao et al. confirmed that NDRG2 was upregulated by p53 or adriamycin (ADR) treatment [10,11]. Thus, NDRG2 can tra...

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Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Cited by 14 publications

References 34 publications

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

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

Emerging role of N-myc downstream-regulated gene 2 (NDRG2) in cancer

N-Myc Downstream-Regulated Gene 2 (NDRG2) as a Novel Tumor Suppressor in Multiple Human Cancers

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