Abstract:
:Previously, we identified the transcription factor CUX1 as an important modulator of invasion and resistance to apoptosis. Expression profiles suggested that CUX1 regulates a complex transcriptional program mediating tumor progression. We aimed to identify functionally relevant targets of CUX1 by using RNA interference (RNAi)-based loss-of-function screens. Therefore, we generated an RNAi library containing putative transcriptional targets of CUX1 identified by microarrays and performed cell viability screens. Using this approach, several CUX1 targets with effect on tumor cell viability were identified, including the glutamate receptor GRIA3, which was validated in detail for its effects on proliferation, apoptosis, and cell migration using RNAi knock-down and overexpression strategies in vitro, as well as xenograft models in vivo. The expression of GRIA3 was evaluated in human pancreatic cancer tissues. We found that knock-down of GRIA3 significantly reduced proliferation and migration and enhanced apoptosis. In contrast, overexpression of GRIA3 significantly reduced apoptosis and enhanced both proliferation and tumor cell migration. GRIA3 could be confirmed as a downstream effector of CUX1 and was expressed in pancreatic cancer tissues. In vivo, GRIA3 significantly enhanced the growth of subcutaneous xenografts. Inhibitors of glutamate receptors such as GYKI52466 and SYM2206 significantly decreased survival of pancreatic cancer cells, suggesting the presence of glutamate signaling in pancreatic cancer. In conclusion, GRIA3 plays a role as a mediator of tumor progression in pancreatic cancer downstream CUX1. To our knowledge, this is the first report to identify a glutamate receptor as a modulator of tumor progression in a solid cancer outside the brain.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Ripka S,Riedel J,Neesse A,Griesmann H,Buchholz M,Ellenrieder V,Moeller F,Barth P,Gress TM,Michl Pdoi
10.1593/neo.10486subject
Has Abstractpub_date
2010-08-01 00:00:00pages
659-67issue
8eissn
1522-8002issn
1476-5586journal_volume
12pub_type
杂志文章相关文献
NEOPLASIA文献大全abstract::The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 co...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900171
更新日期:2001-07-01 00:00:00
abstract::Several observations suggest a potential role of T-cell-mediated immunity in the control of neuroblastoma (NB). However, the generation of NB-specific cytotoxic T lymphocytes (CTL) on T-cell priming with tumor mRNA-transfected dendritic cells (DC) has never been investigated before. In the present study, the feasibili...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06415
更新日期:2006-10-01 00:00:00
abstract::Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor receptor (EGFR) are expressed in several cancers including non-small cell lung cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand, gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of p44/42...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04454
更新日期:2005-04-01 00:00:00
abstract::The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR ta...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2017.02.011
更新日期:2017-05-01 00:00:00
abstract::A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumo...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11400
更新日期:2011-08-01 00:00:00
abstract::The tumor-selective cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) makes TRAIL an attractive candidate as an anticancer agent. However, resistance to TRAIL poses a challenge in anticancer therapy with TRAIL. Therefore, characterizing the mechanisms of resistance and developing stra...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04688
更新日期:2005-06-01 00:00:00
abstract::Numerous human tumor types, including ovarian cancer, display a significant expression of the CD44 family of cell surface proteoglycans. To develop tumor-targeted drugs, we have initially evaluated whether the CD44 ligand hyaluronic acid (HA) could serve as a backbone for paclitaxel (TXL) prodrugs. HA-TXL was prepared...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07229
更新日期:2007-06-01 00:00:00
abstract::Epithelial-myoepithelial carcinoma (EMC) is a rare subtype of salivary gland neoplasms. Since the initial description of the cancer, just over 300 cases have been reported. EMCs occupy a biphasic cellular differentiation-state defined by the constitution of two cell types representing epithelial and myoepithelial line...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2020.06.007
更新日期:2020-09-01 00:00:00
abstract::We examined correlations between TGF-beta1, TbetaR-I and TbetaR-II, p12(CDK2-AP1), p21(WAF1), p27(KIP1), Smad2, and p-Smad2 in 125 cases of human oral squamous cell carcinoma (OSCC) to test the hypothesis that resistance to TGF-beta1-induced growth suppression is due to the disruption of its signaling pathway as a con...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06580
更新日期:2006-12-01 00:00:00
abstract::Transforming growth factor-beta1 (TGF-beta1) can be tumor-suppressive through the activation of the Smad-mediated signaling pathway. TGF-beta1 can also enhance tumor progression by stimulating epithelial-to-mesenchymal transition (EMT) through additional pathways. EMT is characterized by the acquisition of a fibroblas...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.04241
更新日期:2004-09-01 00:00:00
abstract::We report that Binder of Arl Two (BART) plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells. BART was originally identified as a binding partner of ADP-ribosylation factor-like 2, a small G protein implicated as a regulat...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.12352
更新日期:2012-05-01 00:00:00
abstract::The aim of this work was to use phosphorus magnetic resonance spectroscopy ((31)P MRS) to investigate the pharmacodynamic effects of LAQ824, a histone deacetylase (HDAC) inhibitor. Human HT29 colon carcinoma cells were examined by (31)P MRS after treatment with LAQ824 and another HDAC inhibitor, suberoylanilide hydrox...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07834
更新日期:2008-04-01 00:00:00
abstract::Conventional comparative genomic hybridization (CGH) profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80017-9
更新日期:2003-01-01 00:00:00
abstract::We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyr...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111602
更新日期:2012-02-01 00:00:00
abstract::Modulation of the antitumor immune response through the engagement of NKG2D receptors with their ligands (L) on targets represents a promising therapeutic approach against cancer. In this study, we tested the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on the expression of NKG2D ligands in m...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.121236
更新日期:2012-12-01 00:00:00
abstract::Neurofibromatosis type 2 (NF2) is an inherited predisposition cancer syndrome characterized by the development of multiple benign tumors in the nervous system including schwannomas, meningiomas, and ependymomas. Using a disease model comprising primary human schwannoma cells, we previously demonstrated that adherens j...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111060
更新日期:2011-12-01 00:00:00
abstract::Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1593/neo.10290
更新日期:2010-07-01 00:00:00
abstract::With the recent approval of 3 new antibody drug conjugates (ADCs) for solid tumors, this class of drugs is gaining momentum for the targeted treatment of cancer. Despite significant investment, there are still fundamental issues that are incompletely understood. Three of the recently approved ADCs contain payloads exh...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2020.12.001
更新日期:2021-02-01 00:00:00
abstract::Incomplete spontaneous regression of melanoma is common. However, complete melanoma regression is still a very rare phenomenon. Because melanoma is the most immunogenic human malignancy, the mechanisms leading to regression, based on accumulative evidence, are the host's immune responses. Unfortunately, therapies aimi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.08344
更新日期:2008-07-01 00:00:00
abstract::Approximately 50% of prostate cancers harbor the TMPRSS2:ERG fusion, resulting in elevated expression of the ERG transcription factor. Despite the identification of this subclass of prostate cancers, no personalized therapeutic strategies have achieved clinical implementation. Kinases are attractive therapeutic target...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. Although a variety of studies showed the expression of chemokine receptors, in particular, CXCR4, by gastrointestinal tumors, the precise mechanisms of chemokine receptor-mediated homing of c...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.09272
更新日期:2009-07-01 00:00:00
abstract::Signaling events leading to Schwann cell tumor initiation have been extensively characterized in the context of neurofibromatosis (NF). Similar tumors are also observed in patients with the endocrine neoplasia syndrome Carney complex, which results from inactivating mutations in PRKAR1A. Loss of PRKAR1A causes enhance...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.08652
更新日期:2008-11-01 00:00:00
abstract::Head and neck squamous cell carcinomas (HNSCC) are frequently characterized by chemotherapy and radiation resistance, and by overexpression of Bcl-XL, an antiapoptotic member of the Bcl-2 protein family. In this report we examined whether cell-permeable peptides derived from the BH3 domains of proapoptotic Bax, Bad, o...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07394
更新日期:2007-10-01 00:00:00
abstract::p300/CBP-associated factor (PCAF) is a coactivator of the tumor suppressor, p53. PCAF participates in p53's transactivation of target genes through acetylation of both bound p53 and histones within p53 target promoters. Using microarrays, we discovered that PCAF itself is induced by p53 in a panel of breast tumor cell...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.3292
更新日期:2004-05-01 00:00:00
abstract::The infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC), in which HBV X protein (HBx) plays crucial roles. MicroRNAs are involved in diverse biologic functions and in carcinogenesis by regulating gene expression. In the present study, we aim to investigate ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.131362
更新日期:2013-11-01 00:00:00
abstract::Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.101540
更新日期:2011-03-01 00:00:00
abstract::Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast canc...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1016/j.neo.2016.09.002
更新日期:2016-11-01 00:00:00
abstract::A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at differe...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900204
更新日期:2001-11-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in America. Nearly two thirds of newly diagnosed CRC cases include lymph node (LN) involvement, and LN metastasis is one of the strongest negative prognostic factors for CRC. It is thought that CRC tumors ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11324
更新日期:2011-09-01 00:00:00
abstract::Pancreatic cancer patients have an abysmal prognosis because of late diagnosis and lack of therapeutic options. Pancreatic intraepithelial neoplasias (PanINs), the precursor lesions, are a potential target for chemoprevention. Targeting eicosanoid pathways is an obvious choice because 5-lipoxygenase (5-LOX) has been s...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07565
更新日期:2007-11-01 00:00:00