Abstract:
:Tumor suppressor Pdcd4 has recently been shown to inhibit invasion by activating activator protein-1 (AP-1); however, little is known of the functionally significant Pdcd4-target genes. The urokinase receptor (u-PAR) promotes invasion/metastasis, and is associated with poor cancer-patient survival. The present study was conducted (1) to investigate a role for Pdcd4 in intravasation, invasion and u-PAR regulation, and (2) to describe mechanisms by which this is achieved. Fourteen cell lines showed reciprocal expression of u-PAR/Pdcd4. Resected tumor/normal tissues of 29 colorectal cancer patients demonstrated a significant inverse correlation between Pdcd4/u-PAR. siRNA-Pdcd4-transfected GEO cells significantly increased endogenous u-PAR mRNA/protein. A u-PAR-promoter-chloramphenicol acetyl transferase (CAT)-reporter was reduced in activity with increasing Pdcd4 expression in RKO. Deletion of a putative Sp-1-binding site (-402/-350) inhibited u-PAR promoter regulation by Pdcd4, this being paralleled by a reduction of Sp1 binding to this region in pdcd4-transfected cells. Pdcd4-transfected cells showed an increase in Sp3 binding to u-PAR promoter region -152/-135, the deletion of which reduces the ability of Pdcd4 to suppress u-PAR promoter activity. Surprisingly, the u-PAR-AP-1 site was not targeted by Pdcd4. Finally, RKO cells overexpressing Pdcd4 showed an inhibition of invasion/intravasation (chicken embryo metastasis assay). These data suggest Pdcd4 as a new negative regulator of intravasation, and qas the invasion-related gene u-PAR. It is the first study to implicate Pdcd4 regulation of gene expression via Sp1/Sp3.
journal_name
Oncogenejournal_title
Oncogeneauthors
Leupold JH,Yang HS,Colburn NH,Asangani I,Post S,Allgayer Hdoi
10.1038/sj.onc.1210234subject
Has Abstractpub_date
2007-07-05 00:00:00pages
4550-62issue
31eissn
0950-9232issn
1476-5594pii
1210234journal_volume
26pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Topoisomerase IIalpha (topoIIalpha) is an essential mammalian enzyme that topologically modifies DNA and is required for chromosome segregation during mitosis. Previous research suggests that inhibition of topoII decatenatory activity triggers a G(2) checkpoint response, which delays mitotic entry because of insuffici...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.232
更新日期:2010-08-26 00:00:00
abstract::Studies have reported that interactions between keratins (KRTs) and other proteins initiate signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Mo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.221
更新日期:2017-01-19 00:00:00
abstract::In mammalian cells, the p53 protein is a key regulator of the cell cycle following DNA damage. In the present study, we investigated the function of p53 in the A6 amphibian cell line. Using various specific Xenopus p53 monoclonal antibodies, we showed that Xenopus p53 accumulates after DNA damage, including gamma and ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204492
更新日期:2001-06-28 00:00:00
abstract::Lin28b is an RNA-binding protein that inhibits biogenesis of let-7 microRNAs. LIN28B is overexpressed in diverse cancers, yet a specific role in the molecular pathogenesis of colon cancer has to be elucidated. We have determined that human colon tumors exhibit decreased levels of mature let-7 isoforms and increased ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.131
更新日期:2011-10-06 00:00:00
abstract::A new region of the adenovirus E1a protein essential for immortalization and transformation of primary rat kidney cells has been identified. This region is located between amino acid residues 18 to 20 in an N-terminal domain that is not conserved among the various adenovirus serotypes. The transformation defective mut...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-02-01 00:00:00
abstract::Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell li...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.504
更新日期:2016-08-18 00:00:00
abstract::Mutations of SMAD4/DPC4 are found in about 60% of human invasive pancreatic ductal adenocarcinomas (PDACs); yet, the manner in which SMAD4 deficiency enhances tumorigenesis remains elusive. Using a Cre-LoxP approach, we generated a mutant mouse carrying a targeted deletion of Smad4 in the pancreas. We showed that the ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.375
更新日期:2010-02-04 00:00:00
abstract::Mammalian heparanase (endo-beta-glucuronidase) degrades heparan sulfate proteoglycans and is an important modulator of the extracellular matrix and associated factors. The enzyme is preferentially expressed in neoplastic tissues and contributes to tumour metastasis and angiogenesis. To investigate the epigenetic regul...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207056
更新日期:2003-10-30 00:00:00
abstract::From the sequences of Rel/NF-kappa B and I kappa B proteins, we constructed an alignment of their Rel Homology Domain (RHD) and ankyrin repeat domain. Using this alignment, we performed tree reconstruction with both distance matrix and parsimony analysis and estimated the branching robustness using bootstrap resamplin...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201471
更新日期:1997-12-11 00:00:00
abstract::Dysregulation of cellular signaling pathways can lead to colon cancer. However, research on the key signaling effectors or regulators in colon carcinogenesis is limited. Casein kinase-2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is crucial during adult bone formation and is a promising drug target for osteo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.340
更新日期:2014-07-10 00:00:00
abstract::The transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product and related pocket proteins, cyclins and cyclin-dependent kinases. DRTF1/E2F DNA binding activity ari...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-07-06 00:00:00
abstract::Constitutive NF-kappaB activity varies widely among cancer cell lines. In this report, we studied the expression and the role of different I kappaB inhibitors in adenocarcinoma cell lines. High constitutive NF-kappaB activity and low I kappaB-alpha expression was found in a number of these cell lines. Moreover, some o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202599
更新日期:1999-04-22 00:00:00
abstract::Tamoxifen (Tam), besides its action as an anti-estrogen, also inhibits cell proliferation of estrogen receptor (ER)-negative cancer cells by an unknown mechanism. In this study, we used ER-negative lung cancer cells to clarify such ER-independent inhibitory effect of Tam. We found that Tam induced G1 growth arrest in ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202755
更新日期:1999-07-22 00:00:00
abstract::Osteochondroma, the most common benign bone tumor, may occur as a sporadic lesion or as multiple neoplasms in the context of multiple osteochondromas syndrome. The most severe complication is malignant transformation into peripheral secondary chondrosarcoma. Although both benign conditions have been linked to defects ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.135
更新日期:2010-07-01 00:00:00
abstract::Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.599
更新日期:2015-02-05 00:00:00
abstract::Cancer cells lose homeostatic flexibility because of mutations and dysregulated signaling pathways involved in maintaining homeostasis. Tuberous Sclerosis Complex 1 (TSC1) and TSC2 play a fundamental role in cell homeostasis, where signal transduction through TSC1/TSC2 is often compromised in cancer, leading to aberra...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0381-2
更新日期:2018-11-01 00:00:00
abstract::DNA double-stranded breaks (DSBs) elicit a checkpoint response that causes a delay in cell cycle progression. Early in the checkpoint response, histone H2AX is phosphorylated in the chromatin region flanking the DSB by ATM/ATR and DNA-PK kinases. The resulting foci of phosphorylated H2AX (gamma-H2AX) serve as a platfo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.501
更新日期:2010-04-15 00:00:00
abstract::Elucidation of mechanisms underlying the increased androgen receptor (AR) activity and subsequent development of aggressive prostate cancer (PrCa) is pivotal in developing new therapies. Using a systems biology approach, we interrogated the AR-regulated proteome and identified PDZ binding kinase (PBK) as a novel AR-re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0501-z
更新日期:2019-02-01 00:00:00
abstract::Fli-1 is a proto-oncogene which is rearranged in tumors induced by three different retroviruses, Cas-Br-E, F-MuLV, and 10A1. This gene is a member of the Ets gene family, a class of transcription factors that recognize and bind to a DNA motif known as the Ets binding site (EBS). Our laboratory has previously cloned an...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202913
更新日期:1999-09-30 00:00:00
abstract::Cells are under constant attack from genotoxins and rely on a multifaceted DNA damage response (DDR) network to maintain genomic integrity. Central to the DDR are the ATM and ATR kinases, which respond primarily to double-strand DNA breaks (DSBs) and replication stress, respectively. Optimal ATR signaling requires the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.118
更新日期:2016-02-04 00:00:00
abstract::The p53 protein is known to play a central role in mediating G1 arrest or apoptosis in response to ionizing radiation in some cell types. It has been proposed that the link between p53 and induction of apoptosis is provided in part by p53-mediated upregulation of BAX. In this study, we used the human SW626 ovarian can...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201132
更新日期:1997-06-12 00:00:00
abstract::NF-kappaB is known to exert a cytoprotective action against TNF-alpha-induced apoptosis. To study the role of NF-kappaB in various TNF-alpha-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IkappaBalpha inhibitor (MT cells). As NF-kappaB prevented TNF-a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205489
更新日期:2002-05-30 00:00:00
abstract::The translational efficiency of chloramphenicol acetyltransferase (CAT) mRNA containing 5' untranslated region (UTR) sequences of Xenopus c-myc I mRNA was examined in the Xenopus oocyte and early embryo. In contrast to their reduced translation in the oocyte, CAT mRNAs containing 5' UTR sequences located between the c...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Integrin α3β1 regulates adhesive interactions of cells with laminins and have a critical role in adhesion-dependent cellular responses. Here, we examined the role of α3β1-integrin in ErbB2-dependent proliferation of breast cancer cells in three-dimensional laminin-rich extracellular matrix (3D lr-ECM). Depletion of α3...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.231
更新日期:2014-05-22 00:00:00
abstract::To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppres...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-21 00:00:00
abstract::Constitutively active HER2/neu activates nuclear factor kappa-B (NF-kappaB) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor-alpha (TNF-alpha). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediate...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207485
更新日期:2004-05-06 00:00:00
abstract::Histone acetylation has a central role in establishing an active chromatin environment. The functional contribution of histone acetylation to chromatin transcription is accomplished by a dominant action of histone acetyltransferases over repressive histone-modifying activities at gene promoters; misregulation of these...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.273
更新日期:2013-05-16 00:00:00
abstract::Resistance to anti-HER2 (human epithelial growth factor receptor 2) trastuzumab therapy occurs commonly in HER2-positive breast cancer and involves overactivation of HER2 and/or AKT1. Using the model of trastuzumab-sensitive or trastuzumab-resistant HER2-positive cells with wild-type PTEN, negative regulator of AKT1, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.422
更新日期:2010-03-04 00:00:00
abstract::The Li-Fraumeni Syndrome (LFS) is a rare, dominantly inherited syndrome that features high risk of cancers in childhood and early adulthood. Affected families tend to develop bone and soft tissue sarcomas, breast cancers, brain tumors, leukemias, and adrenocortical carcinomas. In some kindreds, the genetic abnormality...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202783
更新日期:1999-07-08 00:00:00
abstract::Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined. O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities. Here, we report that...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0975-3
更新日期:2020-01-01 00:00:00