Endogenous production of leukotriene D4 mediates autocrine survival and proliferation via CysLT1 receptor signalling in intestinal epithelial cells.


:The cysteinyl leukotriene1 (CysLT1) receptor (CysLT1R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour- and tumour-derived intestinal epithelial cells. Treatment of two non-tumour cell lines, Int 407 and IEC-6, with CysLT1R antagonists led to shrinkage and detachment of cells, confirmed as apoptotic cell death, and a dose-dependent reduction in proliferation. However, in the tumour intestinal cell lines Caco-2, SW480, HCT-116 and HT-29, treatment with CysLT1R antagonists significantly reduced proliferation, but had no effect on apoptosis. A unique characteristic of intestinal cancer cells is the presence of nuclear CysLT1Rs, which are inaccessible to receptor antagonists. In these cells, inhibition of the endogenous production of CysLTs indirectly, by 5-lipoxygenase inhibition, impaired CysLT1R signalling throughout the cell, and resulted in apoptosis of the tumour cells. These data reveal the existence of constitutive CysLT1R signalling that mediates both survival and proliferation in intestinal cells. Importantly, we propose that tumour-derived intestinal cells are resistant to CysLT1R antagonist-induced apoptosis, a phenomena that could be explained by nuclear CysLT1R signalling.






Paruchuri S,Mezhybovska M,Juhas M,Sjölander A




Has Abstract


2006-10-26 00:00:00
















  • Cytotoxic drug-induced, p53-mediated upregulation of caspase-8 in tumor cells.

    abstract::Apoptosis resistance is crucially involved in cancer development and progression, represents the leading cause for failure of anticancer therapy and is caused, for example, by downregulation of proapoptotic intracellular signaling molecules such as caspase-8. We found that the cytotoxic drugs methotrexate (MTX) and 5-...


    pub_type: 杂志文章


    authors: Ehrhardt H,Häcker S,Wittmann S,Maurer M,Borkhardt A,Toloczko A,Debatin KM,Fulda S,Jeremias I

    更新日期:2008-01-31 00:00:00

  • Identification of candidate target genes for EVI-1, a zinc finger oncoprotein, using a novel selection strategy.

    abstract::We have sought to identify and isolate target genes for the zinc finger protein, EVI-1, which has been implicated in the genesis of myelogenous leukemia both in mouse and human. We have approached this with a two-step selection: we first selected for genomic fragments of mouse DNA that bind to the protein with high af...


    pub_type: 杂志文章


    authors: Kim JH,Hui P,Yue D,Aycock J,Leclerc C,Bjoring AR,Perkins AS

    更新日期:1998-09-24 00:00:00

  • PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612.

    abstract::Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top...


    pub_type: 杂志文章


    authors: Yang X,Qu S,Wang L,Zhang H,Yang Z,Wang J,Dai B,Tao K,Shang R,Liu Z,Li X,Zhang Z,Xia C,Ma B,Liu W,Li H,Dou K

    更新日期:2018-12-01 00:00:00

  • Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations.

    abstract::An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. He...


    pub_type: 杂志文章


    authors: Lauring J,Cosgrove DP,Fontana S,Gustin JP,Konishi H,Abukhdeir AM,Garay JP,Mohseni M,Wang GM,Higgins MJ,Gorkin D,Reis M,Vogelstein B,Polyak K,Cowherd M,Buckhaults PJ,Park BH

    更新日期:2010-04-22 00:00:00

  • Transcription elongation and eukaryotic gene regulation.

    abstract::Each step in the synthesis of functional transcript by RNA polymerase II provides a level at which gene expression can be regulated. Control over the elongation phase of transcription is a recognized regulatory mechanism in prokaryotes; however, only recently have examples of conditional transcription elongation block...


    pub_type: 杂志文章,评审


    authors: Spencer CA,Groudine M

    更新日期:1990-06-01 00:00:00

  • The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization.

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    pub_type: 杂志文章


    authors: Slee EA,Gillotin S,Bergamaschi D,Royer C,Llanos S,Ali S,Jin B,Trigiante G,Lu X

    更新日期:2004-12-02 00:00:00

  • The FHIT gene is alternatively spliced in normal kidney and renal cell carcinoma.

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    pub_type: 杂志文章


    authors: Luan X,Shi G,Zohouri M,Paradee W,Smith DI,Decker HJ,Cannizzaro LA

    更新日期:1997-07-03 00:00:00

  • PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis.

    abstract::Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regul...


    pub_type: 杂志文章


    authors: Guo Q,Su N,Zhang J,Li X,Miao Z,Wang G,Cheng M,Xu H,Cao L,Li F

    更新日期:2014-06-19 00:00:00

  • Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment.

    abstract::Experimental studies performed prior to 1990 led to the widely held belief that matrix metalloproteinases (MMPs) produced by cancer cells are of critical importance in tumor invasion and metastasis. Based on this evidence, the pharmaceutical industry produced several well tolerated, orally active MMP inhibitors (MMPIs...


    pub_type: 杂志文章,评审


    authors: Zucker S,Cao J,Chen WT

    更新日期:2000-12-27 00:00:00

  • Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer.

    abstract::D-type cyclins are important cell cycle regulators that promote cellular proliferation in response to growth factors by inactivation of the retinoblastoma protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer types and to act as an oncogene in breast cancers. As D-type cyclins are rate limiting ...


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    authors: Russell A,Thompson MA,Hendley J,Trute L,Armes J,Germain D

    更新日期:1999-03-18 00:00:00

  • HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer.

    abstract::Hepatitis B virus (HBV) infection is a major risk factor worldwide for the development of hepatocellular carcinoma (HCC). Integrated HBV DNA fragments, often highly rearranged, are frequently detected in HCC. In woodchuck, the viral enhancer plays a central role in hepatocarcinogenesis, but in humans the mechanism of ...


    pub_type: 杂志文章


    authors: Shamay M,Agami R,Shaul Y

    更新日期:2001-10-18 00:00:00

  • The carboxy terminus of the viral Jun oncoprotein is required for complex formation with the cellular Fos protein.

    abstract::The products of the proto-oncogenes c-jun and c-fos are known to form a complex in vivo. Complex formation appears to stabilize protein-DNA interactions and is thought to play an important functional role in transcriptional regulation. Here we show that the viral Jun oncoprotein, which differs structurally from cellul...


    pub_type: 杂志文章


    authors: Bos TJ,Rauscher FJ 3rd,Curran T,Vogt PK

    更新日期:1989-02-01 00:00:00

  • A role for mismatch repair in control of DNA ploidy following DNA damage.

    abstract::Many reports have shown a link between mismatch repair (MMR) deficiency and loss of normal cell cycle control, particularly loss of G2 arrest. However almost all of these studies utilized transformed cell lines, and thus the involvement of other genes in this phenotype cannot be excluded. We have examined the effects ...


    pub_type: 杂志文章


    authors: Strathdee G,Sansom OJ,Sim A,Clarke AR,Brown R

    更新日期:2001-04-05 00:00:00

  • The human papillomavirus E6 protein and its contribution to malignant progression.

    abstract::The human papillomavirus (HPV) E6 protein is one of three oncoproteins encoded by the virus. It has long been recognized as a potent oncogene and is intimately associated with the events that result in the malignant conversion of virally infected cells. In order to understand the mechanisms by which E6 contributes to ...


    pub_type: 杂志文章,评审


    authors: Mantovani F,Banks L

    更新日期:2001-11-26 00:00:00

  • Decoding whole-genome mutational signatures in 37 human pan-cancers by denoising sparse autoencoder neural network.

    abstract::Millions of somatic mutations have recently been discovered in cancer genomes. These mutations in cancer genomes occur due to internal and external mutagenesis forces. Decoding the mutational processes by examining their unique patterns has successfully revealed many known and novel signatures from whole exome data, b...


    pub_type: 杂志文章


    authors: Pei G,Hu R,Dai Y,Zhao Z,Jia P

    更新日期:2020-07-01 00:00:00

  • Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors.

    abstract::RasGRP1 is a Ras-specific exchange factor, which is activated by T-cell receptor (TCR) and promotes TCR-dependent positive selection of thymocytes. RasGRP1 is highly expressed on most T lymphocytic leukemias and is a common site of proviral insertion in retrovirus-induced murine T-cell lymphomas. We used RasGRP1 trans...


    pub_type: 杂志文章


    authors: Klinger MB,Guilbault B,Goulding RE,Kay RJ

    更新日期:2005-04-14 00:00:00

  • The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration.

    abstract::Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-depende...


    pub_type: 杂志文章


    authors: Saxena M,Dykes SS,Malyarchuk S,Wang AE,Cardelli JA,Pruitt K

    更新日期:2015-01-08 00:00:00

  • Hepatitis B virus X protein promotes the development of liver fibrosis and hepatoma through downregulation of miR-30e targeting P4HA2 mRNA.

    abstract::Hepatitis B virus (HBV)-induced liver necrosis takes great part in liver cirrhosis progression. However, less is known about whether hepatitis B virus X protein (HBx) has effect on liver fibrosis. Here, we report that HBV leads to liver fibrosis and hepatocarcinogenesis through miR-30e targeting P4HA2. HBV transgenic ...


    pub_type: 杂志文章


    authors: Feng GX,Li J,Yang Z,Zhang SQ,Liu YX,Zhang WY,Ye LH,Zhang XD

    更新日期:2017-12-14 00:00:00

  • EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms.

    abstract::Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification a...


    pub_type: 杂志文章


    authors: Del Vecchio CA,Giacomini CP,Vogel H,Jensen KC,Florio T,Merlo A,Pollack JR,Wong AJ

    更新日期:2013-05-23 00:00:00

  • The human A-myb protein is a strong activator of transcription.

    abstract::The A-myb gene belongs to the family of the c-myb proto-oncogene. We report here the cloning from a B lymphocyte cDNA library of the previously missing 3' half of the human A-myb cDNA, thus closing the previously still incomplete open reading frame. Analysis of the homologies between the different myb proteins reveals...


    pub_type: 杂志文章


    authors: Golay J,Loffarelli L,Luppi M,Castellano M,Introna M

    更新日期:1994-09-01 00:00:00

  • MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

    abstract::Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) tha...


    pub_type: 杂志文章


    authors: Chattopadhyay S,Machado-Pinilla R,Manguan-García C,Belda-Iniesta C,Moratilla C,Cejas P,Fresno-Vara JA,de Castro-Carpeño J,Casado E,Nistal M,Gonzalez-Barón M,Perona R

    更新日期:2006-06-01 00:00:00

  • Regulation of fibronectin matrix assembly by activated Ras in transformed cells.

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    pub_type: 杂志文章


    authors: Brenner KA,Corbett SA,Schwarzbauer JE

    更新日期:2000-06-29 00:00:00

  • Importin-β/karyopherin-β1 modulates mitotic microtubule function and taxane sensitivity in cancer cells via its nucleoporin-binding region.

    abstract::The nuclear transport receptor importin-β/karyopherin-β1 is overexpressed in cancers that display genomic instability. It is regarded as a promising cancer target and inhibitors are being developed. In addition to its role in nucleo-cytoplasmic transport, importin-β regulates mitosis, but the programmes and pathways i...


    pub_type: 杂志文章


    authors: Verrico A,Rovella P,Di Francesco L,Damizia M,Staid DS,Le Pera L,Schininà ME,Lavia P

    更新日期:2020-01-01 00:00:00

  • Discordant regulation of SCL/TAL-1 mRNA and protein during erythroid differentiation.

    abstract::The SCL/TAL1 gene was originally identified by virtue of its rearrangement and transcriptional activation in patients with T cell acute lymphoblastic leukaemia. It encodes a helix-loop-helix transcription factor, is not normally expressed in T cells, but is expressed in erythroid, mast, megakaryocytic and progenitor c...


    pub_type: 杂志文章


    authors: Murrell AM,Bockamp EO,Göttgens B,Chan YS,Cross MA,Heyworth CM,Green AR

    更新日期:1995-07-06 00:00:00

  • Introduction of wild-type patched gene suppresses the oncogenic potential of human squamous cell carcinoma cell lines including A431.

    abstract::Defects in a developmental signaling pathway involving the mammalian homologue of the Drosophila segment polarity gene, patched are associated with human tumors such as basal cell carcinoma, medulloblastoma and squamous cell carcinoma. Loss of heterozygosity (LOH) in some of these tumor cells suggests that patched fun...


    pub_type: 杂志文章


    authors: Koike C,Mizutani T,Ito T,Shimizu Y,Yamamichi N,Kameda T,Michimukai E,Kitamura N,Okamoto T,Iba H

    更新日期:2002-04-18 00:00:00

  • Specific DNA binding by different classes of human p53 mutants.

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    pub_type: 杂志文章


    authors: Rolley N,Butcher S,Milner J

    更新日期:1995-08-17 00:00:00

  • Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative transcriptional targets using cDNA microarray expression profiling of genetically defined Wilms' tumors.

    abstract::The Wilms' tumor suppressor gene, WT1, functions as a transcriptional regulator that represses or activates the expression of a variety of putative target genes. However, it is not clear which genes are the biological targets of WT1, nor which cellular pathway(s) is critically altered in tumors as a result of WT1 muta...


    pub_type: 杂志文章


    authors: Udtha M,Lee SJ,Alam R,Coombes K,Huff V

    更新日期:2003-06-12 00:00:00

  • Sequential expression of the MAD family of transcriptional repressors during differentiation and development.

    abstract::Members of the Myc proto-oncogene family encode transcription factors that function in multiple aspects of cell behavior, including proliferation, differentiation, transformation and apoptosis. Recent studies have shown that MYC activities are modulated by a network of nuclear bHLH-Zip proteins. The MAX protein is at ...


    pub_type: 杂志文章


    authors: Quéva C,Hurlin PJ,Foley KP,Eisenman RN

    更新日期:1998-02-26 00:00:00

  • Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase.

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    pub_type: 杂志文章


    authors: Kuo AH,Stoica GE,Riegel AT,Wellstein A

    更新日期:2007-02-08 00:00:00

  • Histone deacetylase associated with mSin3A mediates repression by the acute promyelocytic leukemia-associated PLZF protein.

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    pub_type: 杂志文章


    authors: David G,Alland L,Hong SH,Wong CW,DePinho RA,Dejean A

    更新日期:1998-05-14 00:00:00