Inactivation of ELF/TGF-beta signaling in human gastrointestinal cancer.

Abstract:

:TGF-beta/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. ELF, a beta-spectrin, plays a key role in the transmission of TGF-beta-mediated transcriptional response through Smads. ELF was originally identified as a key protein involved in endodermal stem/progenitor cells committed to foregut lineage. Also, as a major dynamic adaptor and scaffolding protein, ELF is important for the generation of functionally distinct membranes, protein sorting and the development of polarized differentiated epithelial cells. Disruption of elf results in the loss of Smad3/Smad4 activation and, therefore, a disruption of the TGF-beta pathway. These observations led us to pursue the function of ELF in gastrointestinal (GI) epithelial cell-cell adhesion and tumor suppression. Here, we show a significant loss of ELF and reduced Smad4 expression in human gastric cancer tissue samples. Also, of the six human gastric cancer cell lines examined, three show deficient ELF expression. Furthermore, we demonstrate the rescue of E-cadherin-dependent homophilic cell-cell adhesion by ectopic expression of full-length elf. Our results suggest that ELF has an essential role in tumor suppression in GI cancers.

journal_name

Oncogene

journal_title

Oncogene

authors

Katuri V,Tang Y,Marshall B,Rashid A,Jogunoori W,Volpe EA,Sidawy AN,Evans S,Blay J,Gallicano GI,Premkumar Reddy E,Mishra L,Mishra B

doi

10.1038/sj.onc.1208946

subject

Has Abstract

pub_date

2005-12-01 00:00:00

pages

8012-24

issue

54

eissn

0950-9232

issn

1476-5594

pii

1208946

journal_volume

24

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • CCND1 polymorphism and age of onset of hepatoblastoma.

    abstract::Cyclin D1, encoded by the gene CCND1, is a major regulator of the cell cycle transition from G1 phase to S phase. A CCND1 polymorphism (G to A) at codon 242, the boundary of exon 4 and intron 4, affects splicing such that exon 5 is not expressed in the A allele. Since exon 5 is involved in rapid turnover, the variant ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207499

    authors: Pakakasama S,Chen TT,Frawley W,Muller CY,Douglass EC,Lee R,Pollock BH,Tomlinson GE

    更新日期:2004-06-10 00:00:00

  • Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT.

    abstract::Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFβ-dependent biological outputs such as epithelial-mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isof...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.617

    authors: Soond SM,Chantry A

    更新日期:2011-05-26 00:00:00

  • Identification of fyn-encoded proteins in normal human blood cells.

    abstract::We have previously reported that carboxyl terminal truncations of the normal human fyn gene, a member of the src subfamily, can transform immortal mouse fibroblasts to full malignancy. In search of evidence which suggests the possible activation of the human fyn gene, we have screened DNAs and RNAs from a number of hu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Kawakami Y,Furue M,Kawakami T

    更新日期:1989-03-01 00:00:00

  • Targeting Id protein interactions by an engineered HLH domain induces human neuroblastoma cell differentiation.

    abstract::Inhibitor of DNA-binding (Id) proteins prevent cell differentiation, promote growth and sustain tumour development. They do so by binding to E proteins and other transcription factors through the helix-loop-helix (HLH) domain, and inhibiting transcription. This makes HLH-mediated Id protein interactions an appealing t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.56

    authors: Ciarapica R,Annibali D,Raimondi L,Savino M,Nasi S,Rota R

    更新日期:2009-04-30 00:00:00

  • The regulation of translation by the 5' untranslated region of Xenopus c-myc I mRNA during early development.

    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:

    authors: Lazarus P

    更新日期:1992-05-01 00:00:00

  • Paxillin null embryonic stem cells are impaired in cell spreading and tyrosine phosphorylation of focal adhesion kinase.

    abstract::Paxillin is a focal-adhesion associated protein implicated in the regulation of integrin signaling and organization of the actin cytoskeleton. Paxillin associates with numerous signaling molecules including adaptor molecules (p130Cas, CRK), kinases (FAK, Pyk2, PAK and SRC), tyrosine phosphatases (PTP-PEST), ARF-GAP pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205013

    authors: Wade R,Bohl J,Vande Pol S

    更新日期:2002-01-03 00:00:00

  • Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients.

    abstract::Cyr61 is a secreted, cysteine-rich, heparin-binding protein that mediates diverse functions including extracellular matrix formation, differentiation, cell proliferation, adhesion, migration, survival, as well as angiogenesis and tumorigenesis. In this study, we found that Cyr61 gene expression is significantly downre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208550

    authors: Wang B,Ren J,Ooi LL,Chong SS,Lee CG

    更新日期:2005-06-02 00:00:00

  • Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin.

    abstract::Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.377

    authors: Berezov A,Cai Z,Freudenberg JA,Zhang H,Cheng X,Thompson T,Murali R,Greene MI,Wang Q

    更新日期:2012-04-12 00:00:00

  • Beyond the RING: CBL proteins as multivalent adapters.

    abstract::Following discovery of c-Cbl, a cellular form of the transforming retroviral protein v-Cbl, multiple Cbl-related proteins have been identified in vertebrate and invertebrate organisms. c-Cbl and its homologues are capable of interacting with numerous proteins involved in cell signaling, including various molecular ada...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204781

    authors: Tsygankov AY,Teckchandani AM,Feshchenko EA,Swaminathan G

    更新日期:2001-10-01 00:00:00

  • A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways.

    abstract::Earlier we showed that RACK1 regulates growth of human colon cells by suppressing Src activity at G(1) and mitotic checkpoints. Here, we show that RACK1 also induces apoptosis of the cells, partly by inhibiting Src. In the intrinsic pathway, RACK1 inhibits expression of anti-apoptotic Bcl-2 and Bcl-X(L), induces expre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.293

    authors: Mamidipudi V,Cartwright CA

    更新日期:2009-12-17 00:00:00

  • Suppression of proinvasive RGS4 by mTOR inhibition optimizes glioma treatment.

    abstract::An essential mode of acquired resistance to radiotherapy (RT) appears to be promotion of tumor cell motility and invasiveness in various cancer types, including glioblastoma, a process resembling 'evasive resistance'. Hence, a logical advancement of RT would be to identify suitable complementary treatment strategies, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.137

    authors: Weiler M,Pfenning PN,Thiepold AL,Blaes J,Jestaedt L,Gronych J,Dittmann LM,Berger B,Jugold M,Kosch M,Combs SE,von Deimling A,Weller M,Bendszus M,Platten M,Wick W

    更新日期:2013-02-28 00:00:00

  • Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation.

    abstract::The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protei...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210095

    authors: Chikamori M,Fujimoto J,Tokai-Nishizumi N,Yamamoto T

    更新日期:2007-05-03 00:00:00

  • Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer.

    abstract::Oxygen is the ultimate source of oxidizing power for disulfide bond formation, suggesting that under limiting oxygen proper protein folding might be compromised. We show that secretion of vascular endothelial growth factor (VEGF), a protein with multiple disulfide bonds, was indeed impeded under hypoxia and was partia...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208325

    authors: May D,Itin A,Gal O,Kalinski H,Feinstein E,Keshet E

    更新日期:2005-02-03 00:00:00

  • The NF2 tumor suppressor merlin interacts with Ras and RasGAP, which may modulate Ras signaling.

    abstract::Inactivation of the tumor suppressor NF2/merlin underlies neurofibromatosis type 2 (NF2) and some sporadic tumors. Previous studies have established that merlin mediates contact inhibition of proliferation; however, the exact mechanisms remain obscure and multiple pathways have been implicated. We have previously repo...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0883-6

    authors: Cui Y,Groth S,Troutman S,Carlstedt A,Sperka T,Riecken LB,Kissil JL,Jin H,Morrison H

    更新日期:2019-09-01 00:00:00

  • The PGC-1/ERR signaling axis in cancer.

    abstract::Proliferating cells need to produce a large amount of energy and, at the same time, need to maintain a constant supply of biosynthetic precursors of macromolecules that are used as building blocks for generating new cells. Indeed, many cancer cells undergo a switch from mitochondrial to glycolytic metabolism and displ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2012.529

    authors: Deblois G,St-Pierre J,Giguère V

    更新日期:2013-07-25 00:00:00

  • Viral rel and cellular rel associate with cellular proteins in transformed and normal cells.

    abstract::The rel oncogene from the avian reticuloendotheliosis virus strain T is a 59 kd phosphoprotein localized primarily to the cytoplasm of transformed cells. Recently, the v-rel protein was shown to associate with several cellular proteins with molecular weights of 124 kd, 115 kd, and 36 kd. We have analysed the subcellul...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Morrison LE,Kabrun N,Mudri S,Hayman MJ,Enrietto PJ

    更新日期:1989-06-01 00:00:00

  • Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines.

    abstract::We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202317

    authors: Giamarchi C,Solanas M,Chailleux C,Augereau P,Vignon F,Rochefort H,Richard-Foy H

    更新日期:1999-01-14 00:00:00

  • Deficiency of RITA results in multiple mitotic defects by affecting microtubule dynamics.

    abstract::Deregulation of mitotic microtubule (MT) dynamics results in defective spindle assembly and chromosome missegregation, leading further to chromosome instability, a hallmark of tumor cells. RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signaling pathway...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.372

    authors: Steinhäuser K,Klöble P,Kreis NN,Ritter A,Friemel A,Roth S,Reichel JM,Michaelis J,Rieger MA,Louwen F,Oswald F,Yuan J

    更新日期:2017-04-01 00:00:00

  • Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors.

    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 w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210234

    authors: Leupold JH,Yang HS,Colburn NH,Asangani I,Post S,Allgayer H

    更新日期:2007-07-05 00:00:00

  • Polymorphisms in the p53 pathway.

    abstract::The p53 tumor suppressor gene continues to be distinguished as the most frequently mutated gene in human cancer; this gene can be found mutated in up to 50% of human tumors of diverse histological type. It is generally accepted that the ability of p53 to induce either growth arrest or programmed cell death in response...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1209367

    authors: Pietsch EC,Humbey O,Murphy ME

    更新日期:2006-03-13 00:00:00

  • Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.

    abstract::Snail is a zinc finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205416

    authors: Blanco MJ,Moreno-Bueno G,Sarrio D,Locascio A,Cano A,Palacios J,Nieto MA

    更新日期:2002-05-09 00:00:00

  • Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    abstract::Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.519

    authors: Obata Y,Horikawa K,Takahashi T,Akieda Y,Tsujimoto M,Fletcher JA,Esumi H,Nishida T,Abe R

    更新日期:2017-06-29 00:00:00

  • High frequency of p53 protein accumulation without p53 gene mutation in human juvenile pilocytic, low grade and anaplastic astrocytomas.

    abstract::We analysed 31 non-glioblastoma astrocytomas for alterations in p53 protein expression and for mutations in the p53 gene. Immunohistochemistry detected p53 protein accumulation in 71% (five of seven) of juvenile pilocytic astrocytomas (WHO grade I), 63% (five of eight) of astrocytomas (WHO grade II), and 63% (10 of 16...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Lang FF,Miller DC,Pisharody S,Koslow M,Newcomb EW

    更新日期:1994-03-01 00:00:00

  • STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.

    abstract::Mutations in the c-KIT receptor occur somatically in many sporadic Gastrointestinal Stromal Tumors (GIST), and similar mutations have been identified at the germline level in kindreds with multiple GISTs. These mutations activate the tyrosine kinase activity of c-KIT and induce constitutive signaling. To investigate t...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204704

    authors: Tuveson DA,Willis NA,Jacks T,Griffin JD,Singer S,Fletcher CD,Fletcher JA,Demetri GD

    更新日期:2001-08-16 00:00:00

  • CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.

    abstract::CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have sug...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209247

    authors: Dang LH,Chen F,Ying C,Chun SY,Knock SA,Appelman HD,Dang DT

    更新日期:2006-04-06 00:00:00

  • Catch of the day: zebrafish as a human cancer model.

    abstract::Zebrafish are making big waves in the field of cancer research. The effect has been widespread and continues to gain speed as more and more cancer researchers ride the wave of zebrafish biology. This has been largely due to the development of transgenic and xenograft models of cancer, which recapitulate many aspects o...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2008.95

    authors: Stoletov K,Klemke R

    更新日期:2008-07-31 00:00:00

  • Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer.

    abstract::E2F transcription factors are important regulators of the cell cycle, and unrestrained activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. Although highly expressed in normal skin and skin cancer, the role of the atypical E2Fs, E2F7 and E2F8, in keratin...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.251

    authors: Thurlings I,Martínez-López LM,Westendorp B,Zijp M,Kuiper R,Tooten P,Kent LN,Leone G,Vos HJ,Burgering B,de Bruin A

    更新日期:2017-02-09 00:00:00

  • Cellular retinol-binding protein-I inhibits PI3K/Akt signaling through a retinoic acid receptor-dependent mechanism that regulates p85-p110 heterodimerization.

    abstract::Downregulation of the cellular retinol-binding protein-I (CRBP-I) occurs in breast and other human cancers, but its significance is not well understood. Recently, we showed that restoration of CRBP-I expression in transformed MTSV1-7 breast epithelial cells increased retinoic receptor activity, inhibited anoikis, prom...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208347

    authors: Farias EF,Marzan C,Mira-y-Lopez R

    更新日期:2005-02-24 00:00:00

  • A functional analysis of PCNA-binding peptides derived from protein sequence, interaction screening and rational design.

    abstract::Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209320

    authors: Warbrick E

    更新日期:2006-05-11 00:00:00

  • Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene.

    abstract::The onset of human lung cancer occurs through sequential mutations in oncogenes and tumor suppressor genes. Mutations in K-Ras play a prominent role in human non-small cell lung cancer. We have developed a mouse lung tumor model in which K-Ras can be sporadically activated through Cre-lox mediated somatic recombinatio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204837

    authors: Meuwissen R,Linn SC,van der Valk M,Mooi WJ,Berns A

    更新日期:2001-10-04 00:00:00