Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas.

Abstract:

:Malignant glioma represents one of the most aggressive and lethal human neoplasias. A hallmark of gliomas is their rapid proliferation and destruction of vital brain tissue, a process in which excessive glutamate release by glioma cells takes center stage. Pharmacologic antagonism with glutamate signaling through ionotropic glutamate receptors attenuates glioma progression in vivo, indicating that glutamate release by glioma cells is a prerequisite for rapid glioma growth. Glutamate has been suggested to promote glioma cell proliferation in an autocrine or paracrine manner, in particular by activation of the (RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) subtype of glutamate receptors. Here, we dissect the effects of glutamate secretion on glioma progression. Glioma cells release glutamate through the amino-acid antiporter system X(c)(-), a process that is mechanistically linked with cystine incorporation. We show that disrupting glutamate secretion by interfering with the system X(c)(-) activity attenuates glioma cell proliferation solely cystine dependently, whereas glutamate itself does not augment glioma cell growth in vitro. Neither AMPA receptor agonism nor antagonism affects glioma growth in vitro. On a molecular level, AMPA insensitivity is concordant with a pronounced transcriptional downregulation of AMPA receptor subunits or overexpression of the fully edited GluR2 subunit, both of which block receptor activity. Strikingly, AMPA receptor inhibition in tumor-implanted brain slices resulted in markedly reduced tumor progression associated with alleviated neuronal cell death, suggesting that the ability of glutamate to promote glioma progression strictly requires the tumor microenvironment. Concerning a potential pharmacotherapy, targeting system X(c)(-) activity disrupts two major pathophysiological properties of glioma cells, that is, the induction of excitotoxic neuronal cell death and incorporation of cystine required for rapid proliferation.

journal_name

Oncogene

journal_title

Oncogene

authors

Savaskan NE,Seufert S,Hauke J,Tränkle C,Eyüpoglu IY,Hahnen E

doi

10.1038/onc.2010.391

subject

Has Abstract

pub_date

2011-01-06 00:00:00

pages

43-53

issue

1

eissn

0950-9232

issn

1476-5594

pii

onc2010391

journal_volume

30

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Activation of NF-kappa B/Rel by Tax involves degradation of I kappa B alpha and is blocked by a proteasome inhibitor.

    abstract::The tax gene product of the human T-cell leukemia virus type I (HTLV-I) induces the nuclear expression and biological function of the NF-kappa B/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-kappa B/Re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Maggirwar SB,Harhaj E,Sun SC

    更新日期:1995-09-07 00:00:00

  • Isolation of a new class of 'flat' revertants from ras-transformed NIH3T3 cells using cis-4-hydroxy-L-proline.

    abstract::A new class of nontransformed revertant cells has been isolated from the ras-transformed cell line DT using cis-4-hydroxy-L-proline (CHP) as a selective agent. The new revertants, CHP 9CJ and CHP CB4, each contain two copies of the v-Ki-ras gene, elevated levels of phosphorylated p21ras protein, and rescuable transfor...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Yanagihara K,Ciardiello F,Talbot N,McGeady ML,Cooper H,Benade L,Salomon DS,Bassin RH

    更新日期:1990-08-01 00:00:00

  • The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia.

    abstract::Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple relate...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2012.411

    authors: Malek SN

    更新日期:2013-06-06 00:00:00

  • p16MTS1/CDK4I mutations and concomitant loss of heterozygosity at 9p21-23 are frequent events in squamous cell carcinoma of the larynx.

    abstract::We have examined the presence of p16MTS1/CDK4I gene deletions, mutations and methylation status, and 9p21-23 deletions in a series of 46 squamous cell carcinomas of the larynx and paired normal mucosa previously characterized for cyclin D1 gene amplification and overexpression. pRb expression was also examined by immu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201309

    authors: Jares P,Fernández PL,Nadal A,Cazorla M,Hernández L,Pinyol M,Hernández S,Traserra J,Cardesa A,Campo E

    更新日期:1997-09-18 00:00:00

  • Determination of sequences responsible for the differential regulation of Myc function by delta Max and Max.

    abstract::The DNA-binding, transcriptional activation and transforming activities of the Myc protein require dimerization with Max. Max can form also homodimers which are able to bind the same DNA sequence as Myc/Max heterodimers and suppress Myc-induced transcription and transformation. We have recently identified a naturally ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Västrik I,Mäkelä TP,Koskinen PJ,Alitalo K

    更新日期:1995-08-03 00:00:00

  • Determinants of sequence-specific DNA-binding by p48v-myb.

    abstract::The v-myb oncogene of the avian myeloblastosis virus encodes a nuclear protein, p48v-myb, which binds to DNA in a sequence-specific manner. We have used wild type and mutant forms of this protein expressed in E. coli to study the protein and DNA determinants for sequence-specific DNA-binding. We have shown that only t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Garcia A,LaMontagne K,Reavis D,Stober-Grässer U,Lipsick JS

    更新日期:1991-02-01 00:00:00

  • DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo.

    abstract::DAL-1 (differentially expressed in adenocarcinoma of the lung)/4.1B is a tumor suppressor gene on human chromosome 18p11.3 whose expression is lost in >50% of primary non-small-cell lung carcinomas. Based on sequence similarity, DAL-1/4.1B has been assigned to the Protein 4.1 superfamily whose members interact with pl...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208057

    authors: Singh V,Miranda TB,Jiang W,Frankel A,Roemer ME,Robb VA,Gutmann DH,Herschman HR,Clarke S,Newsham IF

    更新日期:2004-10-14 00:00:00

  • Canonical ErbB-2 isoform and ErbB-2 variant c located in the nucleus drive triple negative breast cancer growth.

    abstract::Triple negative breast cancer (TNBC) refers to tumors that do not express clinically significant levels of estrogen and progesterone receptors, and lack membrane overexpression or gene amplification of ErbB-2/HER2, a receptor tyrosine kinase. Transcriptome and proteome heterogeneity of TNBC poses a major challenge to ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-01430-9

    authors: Chervo MF,Cordo Russo RI,Petrillo E,Izzo F,De Martino M,Bellora N,Cenciarini ME,Chiauzzi VA,Santa María de la Parra L,Pereyra MG,Güttlein LN,Podhajcer OL,Daniotti JL,Dupont A,Barchuk S,Figurelli S,Lopez Della Vecchia D,

    更新日期:2020-09-01 00:00:00

  • The Phox2B homeobox gene is mutated in sporadic neuroblastomas.

    abstract::Neuroblastomas are embryonal tumours of the sympatho-adrenal lineage with a clinical course ranging from spontaneous regression to fatal progression. The Phox2B homeobox transcription factor functions in the differentiation of the sympatho-adrenal lineage. Targets of Phox2B are, for example, genes of the (nor)adrenali...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208157

    authors: van Limpt V,Schramm A,van Lakeman A,Sluis P,Chan A,van Noesel M,Baas F,Caron H,Eggert A,Versteeg R

    更新日期:2004-12-09 00:00:00

  • Impairment of antioxidant defense via glutathione depletion sensitizes acute lymphoblastic leukemia cells for Smac mimetic-induced cell death.

    abstract::Evasion of apoptosis in pediatric acute lymphoblastic leukemia (ALL) is linked to aberrant expression of inhibitor of apoptosis (IAP) proteins and dysregulated redox homeostasis, rendering leukemic cells vulnerable to redox-targeting therapies. Here we discover that inhibition of antioxidant defenses via glutathione (...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.338

    authors: Schoeneberger H,Belz K,Schenk B,Fulda S

    更新日期:2015-07-30 00:00:00

  • Myc/miR-378/TOB2/cyclin D1 functional module regulates oncogenic transformation.

    abstract::The c-Myc transcription factor activates a cascade of downstream targets to form a complex transcriptional program that ultimately leads to cellular transformation. Although a large number of protein-encoding genes as well as non-coding RNAs were identified as Myc targets, only a few have been validated to be function...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.602

    authors: Feng M,Li Z,Aau M,Wong CH,Yang X,Yu Q

    更新日期:2011-05-12 00:00:00

  • Concentration-dependent positive and negative regulation of a MAP kinase by a MAP kinase kinase.

    abstract::There are at least three distinct MAP kinase signaling modules in mammalian cells, distinguished by the family of kinases (Erk, SAPK/JNK, or p38) that is ultimately activated. Many input signals activate multiple MAP kinase cascades, and the mechanisms that control the specificity of signal output are not well underst...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203057

    authors: Kieran MW,Katz S,Vail B,Zon LI,Mayer BJ

    更新日期:1999-11-18 00:00:00

  • PU.1 binding to the p53 family of tumor suppressors impairs their transcriptional activity.

    abstract::The transcription factor PU.1 is essential for terminal myeloid differentiation, B- and T-cell development, erythropoiesis and hematopoietic stem cell maintenance. PU.1 functions as oncogene in Friend virus-induced erythroleukemia and as tumor suppressor in acute myeloid leukemias. Moreover, Friend virus-induced eryth...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1211004

    authors: Tschan MP,Reddy VA,Ress A,Arvidsson G,Fey MF,Torbett BE

    更新日期:2008-05-29 00:00:00

  • Mammalian base excision repair by DNA polymerases delta and epsilon.

    abstract::Two distinct pathways for completion of base excision repair (BER) have been discovered in eukaryotes: the DNA polymerase beta (Pol beta)-dependent short-patch pathway that involves the replacement of a single nucleotide and the long-patch pathway that entails the resynthesis of 2-6 nucleotides and requires PCNA. We h...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202001

    authors: Stucki M,Pascucci B,Parlanti E,Fortini P,Wilson SH,Hübscher U,Dogliotti E

    更新日期:1998-08-20 00:00:00

  • NF-kappaB signaling, liver disease and hepatoprotective agents.

    abstract::The NF-kappaB signaling pathway has particular relevance to several liver diseases including hepatitis (liver infection by Helicobacter, viral hepatitis induced by HBV and HCV), liver fibrosis and cirrhosis and hepatocellular carcinoma. Furthermore, the NF-kappaB signaling pathway is a potential target for development...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2008.300

    authors: Sun B,Karin M

    更新日期:2008-10-20 00:00:00

  • Elevated expression of v-mos is correlated with altered differentiation of carcinoma cells.

    abstract::Permanent alterations of the epithelial differentiation pattern were investigated after infection of HH-16 cl. 4 adenocarcinoma cells with Moloney murine sarcoma virus (MoMuSV). Transformed cell clones with fibroblastoid morphology were isolated and compared with clones of unchanged epithelioid phenotype. Southern blo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Scherdin U,Steffen M,Dietel M,Boecker W,Breindl M,Hölzel F

    更新日期:1990-11-01 00:00:00

  • Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity.

    abstract::The FOXO family of Forkhead transcription factors, regulated by the phosphoinositide-3-kinase-Akt pathway, is involved in cell cycle regulation and apoptosis. Strong expression of HER2, a receptor tyrosine kinase oncogene, in cancers has been associated with a poor prognosis. Recently, FOXO4 was shown to regulate the ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208352

    authors: Yang H,Zhao R,Yang HY,Lee MH

    更新日期:2005-03-10 00:00:00

  • Metabolic reprogramming of the tumor.

    abstract::Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a histori...

    journal_title:Oncogene

    pub_type: 历史文章,杂志文章,评审

    doi:10.1038/onc.2011.576

    authors: Ferreira LM,Hebrant A,Dumont JE

    更新日期:2012-09-06 00:00:00

  • LCE: an open web portal to explore gene expression and clinical associations in lung cancer.

    abstract::We constructed a lung cancer-specific database housing expression data and clinical data from over 6700 patients in 56 studies. Expression data from 23 genome-wide platforms were carefully processed and quality controlled, whereas clinical data were standardized and rigorously curated. Empowered by this lung cancer da...

    journal_title:Oncogene

    pub_type: 杂志文章,meta分析

    doi:10.1038/s41388-018-0588-2

    authors: Cai L,Lin S,Girard L,Zhou Y,Yang L,Ci B,Zhou Q,Luo D,Yao B,Tang H,Allen J,Huffman K,Gazdar A,Heymach J,Wistuba I,Xiao G,Minna J,Xie Y

    更新日期:2019-04-01 00:00:00

  • Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma.

    abstract::The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209699

    authors: Mahtouk K,Cremer FW,Rème T,Jourdan M,Baudard M,Moreaux J,Requirand G,Fiol G,De Vos J,Moos M,Quittet P,Goldschmidt H,Rossi JF,Hose D,Klein B

    更新日期:2006-11-16 00:00:00

  • Cellular ITAM-containing proteins are oncoproteins in nonhematopoietic cells.

    abstract::Immunoreceptor tyrosine-based activation motifs (ITAMs) are involved in the transduction of signals necessary for activation, differentiation, and survival in hematopoietic cells. Several viruses have been shown to encode ITAM-containing transmembrane proteins. Although expression of these viral proteins has in some c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209296

    authors: Grande SM,Katz E,Crowley JE,Bernardini MS,Ross SR,Monroe JG

    更新日期:2006-05-04 00:00:00

  • Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex.

    abstract::Collagenase1 (MMP1) and stromelysin1 (MMP3) are extracellular proteolytic enzymes that degrade connective tissue macromolecules and basement membranes. Both genes are regulated by the Ets and Fos/Jun families of transcription factors/oncoproteins. Here, we show that two members of the Ets-family, Ets2 and Erg and thei...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Butticè G,Duterque-Coquillaud M,Basuyaux JP,Carrère S,Kurkinen M,Stéhelin D

    更新日期:1996-12-05 00:00:00

  • Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis.

    abstract::To identify genes that are differentially over-expressed in Small Cell Lung Carcinoma (SCLC) we have used a combination of suppression subtractive hybridization and cDNA microarray to analyse the expression profiles of 2400 cDNAs clones. Genes that are over-expressed in SCLC were identified using 32 pairs of fluoresce...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205480

    authors: Bangur CS,Switzer A,Fan L,Marton MJ,Meyer MR,Wang T

    更新日期:2002-05-23 00:00:00

  • Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.

    abstract::Low oxygen tension (hypoxia) is a common feature of solid tumors and stimulates the expressions of a variety of genes including those related to angiogenesis, apoptosis and endoplasmic reticulum (ER) stress response. Here we show a close correlation between metastatic potential and the resistance to hypoxia- and ER st...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209128

    authors: Koshikawa N,Maejima C,Miyazaki K,Nakagawara A,Takenaga K

    更新日期:2006-02-09 00:00:00

  • U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia.

    abstract::Upregulated gene 19 (U19)/ELL-associated factor 2 (Eaf2) is a potential human tumor suppressor that exhibits frequent allelic loss and downregulation in high-grade prostate cancer. U19/Eaf2, along with its homolog Eaf1, has been reported to regulate transcriptional elongation via interaction with the eleven-nineteen l...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210786

    authors: Xiao W,Zhang Q,Habermacher G,Yang X,Zhang AY,Cai X,Hahn J,Liu J,Pins M,Doglio L,Dhir R,Gingrich J,Wang Z

    更新日期:2008-03-06 00:00:00

  • Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role of the chromatin structure and AP-1 composition.

    abstract::The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts. In contrast, MCP-1 transcription is absent in tumor...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203643

    authors: Finzer P,Soto U,Delius H,Patzelt A,Coy JF,Poustka A,zur Hausen H,Rösl F

    更新日期:2000-07-06 00:00:00

  • Random mutagenesis of PDZ(Omi) domain and selection of mutants that specifically bind the Myc proto-oncogene and induce apoptosis.

    abstract::Omi is a mammalian serine protease that is localized in the mitochondria and released to the cytoplasm in response to apoptotic stimuli. Omi induces cell death in a caspase-dependent manner by interacting with the X-chromosome linked inhibitor of apoptosis protein, as well as in a caspase-independent way that relies o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206359

    authors: Junqueira D,Cilenti L,Musumeci L,Sedivy JM,Zervos AS

    更新日期:2003-05-08 00:00:00

  • CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development.

    abstract::Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT com...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0603-7

    authors: Shirai YT,Mizutani A,Nishijima S,Horie M,Kikuguchi C,Elisseeva O,Yamamoto T

    更新日期:2019-04-01 00:00:00

  • Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells.

    abstract::Squamous cell carcinoma (SCC) cells of the head and neck specifically express collagenase-3 (matrix metalloproteinase-13 (MMP-13)), the expression of which correlates with their invasion capacity. Transforming growth factor-beta (TGF-beta) enhances MMP-13 and collagenase-1 (MMP-1) expression and invasion of SCC cells ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209291

    authors: Leivonen SK,Ala-Aho R,Koli K,Grénman R,Peltonen J,Kähäri VM

    更新日期:2006-04-27 00:00:00

  • KLF10 loss in the pancreas provokes activation of SDF-1 and induces distant metastases of pancreatic ductal adenocarcinoma in the KrasG12D p53flox/flox model.

    abstract::Krüppel-like transcription factor 10 (KLF10), also named as TIEG1, plays essential roles in mediating transforming growth factor beta (TGFβ) signaling and has been shown to function as a tumor suppressor in multiple cancer types. However, its roles in mediating cancer progression in vivo have yet to be fully character...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.155

    authors: Weng CC,Hawse JR,Subramaniam M,Chang VHS,Yu WCY,Hung WC,Chen LT,Cheng KH

    更新日期:2017-09-28 00:00:00