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https://www.readbyqxmd.com/read/28803608/identification-of-simvastatin-regulated-targets-associated-with-jnk-activation-in-du145-human-prostate-cancer-cell-death-signaling
#1
Eun Joo Jung, Ky Hyun Chung, Choong Won Kim
In this study, our results showed that the c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1) and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways...
August 11, 2017: BMB Reports
https://www.readbyqxmd.com/read/28776325/identification-and-functional-characterization-of-two-missense-mutations-in-ndrg1-associated-with-charcot-marie-tooth-disease-type-4d-cmt4d
#2
Li-Xi Li, Gong-Lu Liu, Zhi-Jun Liu, Cong Lu, Zhi-Ying Wu
Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 - c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6-8 - have been described in CMT4D patients. Here, using targeted next-generation sequencing (NGS) examination, we identified for the first time two homozygous missense variants in NDRG1, c...
August 3, 2017: Human Mutation
https://www.readbyqxmd.com/read/28775290/ndrg1-promotes-adipocyte-differentiation-and-sustains-their-function
#3
Kai Cai, Rabih El-Merahbi, Mona Loeffler, Alexander E Mayer, Grzegorz Sumara
Adipocytes play a central role in maintaining metabolic homeostasis in the body. Differentiation of adipocyte precursor cells requires the transcriptional activity of peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding proteins (C/Ebps). Transcriptional activity is regulated by signaling modules activated by a plethora of hormones and nutrients. Mechanistic target of rapamacin complexes (mTORC) 1 and 2 are central for the coordination of hormonal and nutritional inputs in cells and are essential for adipogenesis...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775238/n-myc-downstream-regulated-gene-1-promotes-apoptosis-in-colorectal-cancer-via-up-regulating-death-receptor-4
#4
Xian Zhang, Bo Feng, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Meng Pan, Zirui He, Xiongzhi Wangpu, Jing Sun, Xiao Yang
The aim of this study was to evaluate the clinical significance of N-myc downstream-regulated gene 1 (NDRG1) in colorectal cancer (CRC) patients and to explore the mechanisms governing the role of NDRG1 in apoptosis of CRC cells. In the current study, we found that NDRG1 was a prognostic marker of CRC patients. Moreover, NDRG1 expression negatively correlated to tumor size and clinical TNM stage, suggesting that NDRG1 might act as a tumor suppressor by inhibiting proliferation or inducing apoptosis in CRC. Consistently, substantial apoptosis was observed in vitro and in vivo in the presence of NDRG1...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701735/quantitative-proteomics-reveal-the-anti-tumour-mechanism-of-the-carbohydrate-recognition-domain-of-galectin-3-in-hepatocellular-carcinoma
#5
Mingchao Wang, Fang Tian, Wantao Ying, Xiaohong Qian
Hepatocellular carcinoma (HCC) is a serious threat to human health. The carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC and its possible molecular mechanism with quantitative proteomics approach. We found that rGal3C stimulation could inhibit cell viability, migration and invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially expressed. Eighty up-regulated proteins located mainly in extracellular exosome and involved in cell adhesion and metabolism, and 110 down-regulated proteins located in mitochondria and extracellular exosome, and related to processes of metabolism and oxidation-reduction...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615452/interplay-of-the-iron-regulated-metastasis-suppressor-ndrg1-with-epidermal-growth-factor-receptor-egfr-and-oncogenic-signaling
#6
REVIEW
Sharleen V Menezes, Sumit Sahni, Zaklina Kovacevic, Des R Richardson
The iron-regulated metastasis suppressor N-myc downstream-regulated gene 1 (NDRG1) has been shown to inhibit numerous oncogenic signaling pathways in cancer cells. Recent findings have demonstrated that NDRG1 inhibits the ErbB family of receptors, which function as key inducers of carcinogenesis. NDRG1 attenuates ErbB signaling by inhibiting formation of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) and HER2/HER3 heterodimers and by down-regulating EGFR via a mechanism involving its degradation...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545025/oncogenic-mnk-signalling-regulates-the-metastasis-suppressor-ndrg1
#7
Shuye Tian, Xuemin Wang, Christopher G Proud
The protein N-myc down-regulated gene 1 (NDRG1) represses tumour metastasis. It is phosphorylated at several sites by serum and glucocorticoid-regulated kinase 1 (SGK1). Here we show that NDRG1 is also regulated by the oncogenic MAP kinase-interacting kinase (MNK) pathway, a target for cancer therapy.Inhibiting MNKs increases the expression of NDRG1 protein and mRNA in breast cancer cells. MNK inhibition also decreases the phosphorylation of NDRG1. Phosphorylation of NDRG1 is reduced in cells lacking MNK1, but not MNK2-knockout cells, indicating that NDRG1 phosphorylation is a specific target for MNK1...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537875/n-myc-downstream-regulated-gene-1-promotes-oxaliplatin-triggered-apoptosis-in-colorectal-cancer-cells-via-enhancing-the-ubiquitination-of-bcl-2
#8
Xiao Yang, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Luyang Zhang, Yanfeng Lv, Jing Sun, Minhua Zheng
N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521460/n-myc-downstream-regulated-gene-1-inhibits-the-proliferation-and-invasion-of-hepatocellular-carcinoma-cells-via-the-regulation-of-integrin-%C3%AE-3
#9
Yan Song, Guangping Wu, Mingyang Zhang, Qianqian Kong, Juan Du, Yabing Zheng, Longtao Yue, Lili Cao
N-myc downstream-regulated gene 1 (NDRG1) is a multifunctional protein associated with carcinogenesis and tumor progression. The function of NDRG1 in hepatocellular carcinoma (HCC) cells remains controversial. The present study investigated the role of NDRG1 in HCC as well as its molecular mechanism using a range of techniques, including western blot analysis, cellular proliferation test, wound healing assay and Transwell assay. In HCC, the levels of NDRG1 expression were highest in the cytoplasm, followed by the membrane, and were lowest in the nucleus...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28509555/differential-phosphoproteomic-analysis-of-recombinant-chinese-hamster-ovary-cells-following-temperature-shift
#10
Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes, including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis, and signal transduction. However, to date, little work has been carried out on the phosphoproteome in CHO cells. In this study we have carried out a large scale differential phosphoproteomic analysis of recombinant CHO cells following a reduction of culture temperature (temperature shift)...
June 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28506304/characterization-of-genetic-aberrations-in-a-single-case-of-metastatic-thymic-adenocarcinoma
#11
Yeonghun Lee, Sehhoon Park, Se-Hoon Lee, Hyunju Lee
BACKGROUND: Thymic adenocarcinoma is an extremely rare subtype of thymic epithelial tumors. Due to its rarity, there is currently no sequencing approach for thymic adenocarcinoma. METHODS: We performed whole exome and transcriptome sequencing on a case of thymic adenocarcinoma and performed subsequent validation using Sanger sequencing. RESULTS: The case of thymic adenocarcinoma showed aggressive behaviors with systemic bone metastases. We identified a high incidence of genetic aberrations, which included somatic mutations in RNASEL, PEG10, TNFSF15, TP53, TGFB2, and FAT1...
May 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28498432/time-%C3%A2-and-oxygen-dependent-expression-and-regulation-of-ndrg1-in-human-brain-cancer-cells
#12
Harun Muayad Said, Roghaiyeh Safari, Ghada Al-Kafaji, Ralf-Ingo Ernestus, Mario Löhr, Astrid Katzer, Michael Flentje, Carsten Hagemann
N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28464941/re-emergence-of-hereditary-polyneuropathy-in-scandinavian-alaskan-malamute-dogs-old-enemy-or-new-entity-a-case-series
#13
Karin Hultin Jäderlund, Cecilia Rohdin, Mette Berendt, Øyvind Stigen, Merete Fredholm, Arild Espenes, Inge Bjerkås, Lars Moe
A homozygous mutation has been identified in the N-myc downstream-regulated gene 1 (NDRG1) in recent cases of polyneuropathy in Alaskan malamute dogs from the Nordic countries and USA. The objective of the present study was to determine if cases diagnosed 30-40 years ago with polyneuropathy in the Alaskan malamute breed in Norway had the same hereditary disease as the recent cases. Fourteen historical cases and 12 recently diagnosed Alaskan malamute dogs with hereditary polyneuropathy, and their parents and littermates (n = 88) were included in this study (total n = 114)...
May 2, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28464351/mammalian-target-of-rapamycin-complex-2-regulates-muscle-glucose-uptake-during-exercise-in-mice
#14
Maximilian Kleinert, Benjamin L Parker, Andreas M Fritzen, Jonas R Knudsen, Thomas E Jensen, Rasmus Kjøbsted, Lykke Sylow, Markus Ruegg, David E James, Erik A Richter
KEY POINTS: Exercise is a potent physiological stimulus to clear blood glucose from the circulation into skeletal muscle. The mammalian target of rapamycin complex 2 (mTORC2) is an important regulator of muscle glucose uptake in response to insulin stimulation. Here we report for the first time that the activity of mTORC2 in mouse muscle increases during exercise. We further show that glucose uptake during exercise is decreased in mouse muscle that lacks mTORC2 activity. We also provide novel identifications of new mTORC2 substrates during exercise in mouse muscle...
July 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28456659/n-myc-downstream-regulated-gene-1-ndrg1-promotes-the-stem-like-properties-of-lung-cancer-cells-through-stabilized-c-myc
#15
Yongfang Wang, You Zhou, Feng Tao, Shoujie Chai, Xia Xu, Ying Yang, Yiming Yang, Haiyan Xu, Kai Wang
Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC...
April 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28453552/specific-blockade-of-rictor-mtor-association-inhibits-mtorc2-activity-and-is-cytotoxic-in-glioblastoma
#16
Angelica Benavides-Serrato, Jihye Lee, Brent Holmes, Kenna A Landon, Tariq Bashir, Michael E Jung, Alan Lichtenstein, Joseph Gera
A small molecule which specifically blocks the interaction of Rictor and mTOR was identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations and in cellular assays specifically inhibited phosphorylation of mTORC2 substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCα (Ser-657), while having no appreciable effects on the phosphorylation status of the mTORC1 substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops...
2017: PloS One
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#17
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376589/-expression-characteristics-of-pten-and-ndrg1-in-colorectal-carcinoma-and-their-prognostic-value
#18
G X Zhang, Z Y Qian, L J Yang, F Wang, H Shen
Objective: To study the expression status and clinical significance of PTEN and NDRG1 in colorectal carcinoma. Methods: Tissue samples of 91 colorectal cancers, 30 colorectal adenomas and 21 colorectal normal mucosa tissues were collected. Postoperative specimens were examined by immunohistochemistry for PTEN and NDRG1 expression. The expression of PTEN and NDRG1 was correlated with clinicopathological feature. Results: The expression of PTEN and NDRG1 in the studied cases was detected in 55.0%(50/91) and 76...
April 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28371345/the-prostate-metastasis-suppressor-gene-ndrg1-differentially-regulates-cell-motility-and-invasion
#19
Anup Sharma, Janet Mendonca, James Ying, Hea-Soo Kim, James E Verdone, Jelani C Zarif, Michael Carducci, Hans Hammers, Kenneth J Pienta, Sushant Kachhap
Experimental and clinical evidence suggests that N-myc downregulated gene 1 (NDRG1) functions as a suppressor of prostate cancer metastasis. Elucidating pathways that drive survival and invasiveness of NDRG1-deficient prostate cancer cells can help in designing therapeutics to target metastatic prostate cancer cells. However, the molecular mechanisms that lead NDRG1-deficient prostate cancer cells to increased invasiveness remain largely unknown. In this study, we demonstrate that NDRG1-deficient prostate tumors have decreased integrin expression and reduced cell adhesion and motility...
June 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28350132/a-new-facet-of-ndrg1-in-pancreatic-ductal-adenocarcinoma-suppression-of-glycolytic-metabolism
#20
Wensheng Liu, Bo Zhang, Qiangsheng Hu, Yi Qin, Wenyan Xu, Si Shi, Chen Liang, Qingcai Meng, Jinfeng Xiang, Dingkong Liang, Shunrong Ji, Jiang Liu, Pengfei Hu, Liang Liu, Chen Liu, Jiang Long, Quanxing Ni, Xianjun Yu, Jin Xu
N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1α level...
May 2017: International Journal of Oncology
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