Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition.

Abstract:

:Sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) glycans are expressed on highly metastatic colon cancer cells. They promote extravasation of cancer cells and tumor angiogenesis via interacting with E-selectin on endothelial cells. Recently, epithelial-mesenchymal transition (EMT) has been noted as a critical phenotypic alteration in metastatic cancer cells. To address the association between sLe(x/a) expression and EMT, we assessed whether sLe(x/a) are highly expressed on colon cancer cells undergoing EMT. Treatment of HT29 and DLD-1 cells with EGF and/or basic FGF (bFGF) induced EMT and significantly increased sLe(x/a) expression resulting in enhanced E-selectin binding activity. The transcript levels of the glycosyltransferase genes ST3GAL1/3/4 and FUT3 were significantly elevated and that of FUT2 was significantly suppressed by the treatment. We provide evidence that ST3GAL1/3/4 and FUT3 are transcriptionally up-regulated by c-Myc with probable involvement of Ser62 phosphorylation, and that FUT2 is transcriptionally down-regulated through the attenuation of CDX2. The contribution of c-Myc and CDX2 to the sLe(x/a) induction was proved to be significant by knockdown or forced expression experiments. Interestingly, the cells undergoing EMT exhibited significantly increased VEGF secretion, which can promote tumor angiogenesis in cooperation with sLe(x/a). Finally, immunohistological study indicated high E-selectin ligand expression on cancer cells undergoing EMT in vivo, supporting their coexistence observed in vitro. These results suggest a significant link between sLe(x/a) expression and EMT in colon cancer cells and a pivotal role of c-Myc and CDX2 in regulating sLe(x/a) expression during EMT.

authors

Sakuma K,Aoki M,Kannagi R

doi

10.1073/pnas.1111135109

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

7776-81

issue

20

eissn

0027-8424

issn

1091-6490

pii

1111135109

journal_volume

109

pub_type

杂志文章
  • A common allosteric site and mechanism in caspases.

    abstract::We present a common allosteric mechanism for control of inflammatory and apoptotic caspases. Highly specific thiol-containing inhibitors of the human inflammatory caspase-1 were identified by using disulfide trapping, a method for site-directed small-molecule discovery. These compounds became trapped by forming a disu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602571103

    authors: Scheer JM,Romanowski MJ,Wells JA

    更新日期:2006-05-16 00:00:00

  • Aminofluorene-DNA adduct formation in Salmonella typhimurium exposed to the carcinogen N-hydroxy-2-acetylaminofluorene.

    abstract::The DNA adducts formed during incubation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene with Salmonella typhimurium tester strain TA1538 were investigated to determine if the covalently bound products were identical to those adducts found in rat liver DNA and to establish the biological significance of the ad...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.17.5175

    authors: Beranek DT,White GL,Heflich RH,Beland FA

    更新日期:1982-09-01 00:00:00

  • Hidden resources in the Escherichia coli genome restore PLP synthesis and robust growth after deletion of the essential gene pdxB.

    abstract::PdxB (erythronate 4-phosphate dehydrogenase) is expected to be required for synthesis of the essential cofactor pyridoxal 5'-phosphate (PLP) in Escherichia coli Surprisingly, incubation of the ∆pdxB strain in medium containing glucose as a sole carbon source for 10 d resulted in visible turbidity, suggesting that PLP ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1915569116

    authors: Kim J,Flood JJ,Kristofich MR,Gidfar C,Morgenthaler AB,Fuhrer T,Sauer U,Snyder D,Cooper VS,Ebmeier CC,Old WM,Copley SD

    更新日期:2019-11-26 00:00:00

  • Adaptive climatic molecular evolution in wild barley at the Isa defense locus.

    abstract::Wild barley (Hordeum spontaneum) represents a significant genetic resource for crop improvement in barley (Hordeum vulgare) and for the study of the evolution and domestication of plant populations. The Isa gene from barley has a putative role in plant defense. This gene encodes a bifunctional alpha-amylase/subtilisin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611226104

    authors: Cronin JK,Bundock PC,Henry RJ,Nevo E

    更新日期:2007-02-20 00:00:00

  • Interaction of a common cellular transcription factor, ATF, with regulatory elements in both E1a- and cyclic AMP-inducible promoters.

    abstract::We have previously identified a cellular transcription factor, ATF, which is involved in the expression of multiple adenovirus E1a-inducible genes. Here we show that ATF also binds to regulatory elements in cellular cAMP-inducible promoters. In these cellular promoters, ATF binds to a consensus sequence that has been ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.10.3396

    authors: Lin YS,Green MR

    更新日期:1988-05-01 00:00:00

  • Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism.

    abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-rib...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.10.5774

    authors: Mandir AS,Przedborski S,Jackson-Lewis V,Wang ZQ,Simbulan-Rosenthal CM,Smulson ME,Hoffman BE,Guastella DB,Dawson VL,Dawson TM

    更新日期:1999-05-11 00:00:00

  • Site-specific effect of thymine dimer formation on dAn.dTn tract bending and its biological implications.

    abstract::dAn.dTn sequences, otherwise known as A tracts, are hotspots for cis-syn thymine dimer formation and deletion mutations induced by UV light. Such A tracts are also known to bend DNA, suggesting that some biological effects of UV light might be related to the distinctive structure and properties of cis-syn dimer-contai...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.20.9072

    authors: Wang CI,Taylor JS

    更新日期:1991-10-15 00:00:00

  • Specificity landscapes unmask submaximal binding site preferences of transcription factors.

    abstract::We have developed Differential Specificity and Energy Landscape (DiSEL) analysis to comprehensively compare DNA-protein interactomes (DPIs) obtained by high-throughput experimental platforms and cutting edge computational methods. While high-affinity DNA binding sites are identified by most methods, DiSEL uncovered nu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1811431115

    authors: Bhimsaria D,Rodríguez-Martínez JA,Pan J,Roston D,Korkmaz EN,Cui Q,Ramanathan P,Ansari AZ

    更新日期:2018-11-06 00:00:00

  • Time-resolved infrared (TRIR) study on the formation and reactivity of organometallic methane and ethane complexes in room temperature solution.

    abstract::We have used fast time-resolved infrared spectroscopy to characterize a series of organometallic methane and ethane complexes in solution at room temperature: W(CO)5(CH4) and M(eta5-C5R5)(CO)2(L) [where M = Mn or Re, R = H or CH3 (Re only); and L = CH4 or C2H6]. In all cases, the methane complexes are found to be shor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0610567104

    authors: Cowan AJ,Portius P,Kawanami HK,Jina OS,Grills DC,Sun XZ,McMaster J,George MW

    更新日期:2007-04-24 00:00:00

  • Proton shuttle in green fluorescent protein studied by dynamic simulations.

    abstract::As a direct simulation of a multistep proton transfer reaction involving protein residues, the proton relay shuttle between A and I forms of green fluorescent protein (GFP) is simulated in atomic detail by using a special molecular dynamics simulation technique. Electronic excitation of neutral chromophore in wild-typ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.052520799

    authors: Lill MA,Helms V

    更新日期:2002-03-05 00:00:00

  • Two distinctly regulated events, priming and triggering, during retinoid-induced maturation and resistance of NB4 promyelocytic leukemia cell line.

    abstract::In t(15;17) acute promyelocytic leukemia, all-trans retinoic acid (RA) induces leukemic cell maturation in vitro and remission in acute promyelocytic leukemia patients, but in vivo treatments invariably lead to relapse with resistance to RA. NB4, a maturation-inducible cell line, and NB4-RAr sublines (R1 and R2) displ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.18.8428

    authors: Ruchaud S,Duprez E,Gendron MC,Houge G,Genieser HG,Jastorff B,Doskeland SO,Lanotte M

    更新日期:1994-08-30 00:00:00

  • Monoclonal antibody-superantigen fusion proteins: tumor-specific agents for T-cell-based tumor therapy.

    abstract::The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we have made a recombinant fusion protein of SEA and the Fab region o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.19.8945

    authors: Dohlsten M,Abrahmsén L,Björk P,Lando PA,Hedlund G,Forsberg G,Brodin T,Gascoigne NR,Förberg C,Lind P

    更新日期:1994-09-13 00:00:00

  • Mechanism by which a recently discovered allosteric inhibitor blocks glutamine metabolism in transformed cells.

    abstract::The mitochondrial enzyme glutaminase C (GAC) catalyzes the hydrolysis of glutamine to glutamate plus ammonia, a key step in the metabolism of glutamine by cancer cells. Recently, we discovered a class of allosteric inhibitors of GAC that inhibit cancer cell growth without affecting their normal cellular counterparts, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1414056112

    authors: Stalnecker CA,Ulrich SM,Li Y,Ramachandran S,McBrayer MK,DeBerardinis RJ,Cerione RA,Erickson JW

    更新日期:2015-01-13 00:00:00

  • Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase.

    abstract::Smad proteins are key intracellular signaling effectors for the transforming growth factor-beta superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tightly regulated to...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.98.3.974

    authors: Zhang Y,Chang C,Gehling DJ,Hemmati-Brivanlou A,Derynck R

    更新日期:2001-01-30 00:00:00

  • Evolutionary switches between two serine codon sets are driven by selection.

    abstract::Serine is the only amino acid that is encoded by two disjoint codon sets so that a tandem substitution of two nucleotides is required to switch between the two sets. Previously published evidence suggests that, for the most evolutionarily conserved serines, the codon set switch occurs by simultaneous substitution of t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1615832113

    authors: Rogozin IB,Belinky F,Pavlenko V,Shabalina SA,Kristensen DM,Koonin EV

    更新日期:2016-11-15 00:00:00

  • Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene.

    abstract::Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of gene...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0503039102

    authors: Borrello MG,Alberti L,Fischer A,Degl'innocenti D,Ferrario C,Gariboldi M,Marchesi F,Allavena P,Greco A,Collini P,Pilotti S,Cassinelli G,Bressan P,Fugazzola L,Mantovani A,Pierotti MA

    更新日期:2005-10-11 00:00:00

  • Ecosystem recovery after climatic extremes enhanced by genotypic diversity.

    abstract::Contemporary climate change is characterized both by increasing mean temperature and increasing climate variability such as heat waves, storms, and floods. How populations and communities cope with such climatic extremes is a question central to contemporary ecology and biodiversity conservation. Previous work has sho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0500008102

    authors: Reusch TB,Ehlers A,Hämmerli A,Worm B

    更新日期:2005-02-22 00:00:00

  • PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of DsbA.

    abstract::Adhesive P pili of uropathogenic Escherichia coli were not assembled by a strain that lacks the periplasmic disulfide isomerase DsbA. This defect was mostly attributed to the immunoglobulin-like pilus chaperone PapD, which possesses an unusual intrasheet disulfide bond between the last two beta-strands of its CD4-like...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.24.11552

    authors: Jacob-Dubuisson F,Pinkner J,Xu Z,Striker R,Padmanhaban A,Hultgren SJ

    更新日期:1994-11-22 00:00:00

  • Metaphase and interphase fluorescence in situ hybridization mapping of the rice genome with bacterial artificial chromosomes.

    abstract::Fluorescence in situ hybridization (FISH) is a powerful tool for physical mapping in human and other mammalian species. However, application of the FISH technique has been limited in plant species, especially for mapping single- or low-copy DNA sequences, due to inconsistent signal production in plant chromosome prepa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.10.4487

    authors: Jiang J,Gill BS,Wang GL,Ronald PC,Ward DC

    更新日期:1995-05-09 00:00:00

  • Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme.

    abstract::Two functional human dUTP pyrophosphatase (dUTPase; EC 3.6.1.23) cDNAs were isolated from a cDNA expression library by genetic complementation in Escherichia coli. These cDNAs differed in size but exhibited a common overlapping DNA sequence. Contained within this sequence was a single long open reading frame sufficien...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.8020

    authors: McIntosh EM,Ager DD,Gadsden MH,Haynes RH

    更新日期:1992-09-01 00:00:00

  • Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.

    abstract::Following proteolytic conversion of fibrinogen to fibrin, clot assembly commences with formation of double-stranded fibrils that subsequently branch extensively in forming a three-dimensional network. Plasmin digests of fibrin clots that had first been covalently crosslinked by plasma transglutaminase (factor XIIIa) c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.4.1113

    authors: Mosesson MW,Siebenlist KR,Amrani DL,DiOrio JP

    更新日期:1989-02-01 00:00:00

  • Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3.

    abstract::Salt and water secretion from intestinal epithelia requires enhancement of anion permeability across the apical membrane of Cl- secreting cells lining the crypt, the secretory gland of the intestine. Paneth cells located at the base of the small intestinal crypt release enteric defensins (cryptdins) apically into the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.16.8585

    authors: Lencer WI,Cheung G,Strohmeier GR,Currie MG,Ouellette AJ,Selsted ME,Madara JL

    更新日期:1997-08-05 00:00:00

  • Circadian-independent cell mitosis in immortalized fibroblasts.

    abstract::Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhyth...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914078107

    authors: Yeom M,Pendergast JS,Ohmiya Y,Yamazaki S

    更新日期:2010-05-25 00:00:00

  • A predictive, size-dependent continuum model for dense granular flows.

    abstract::Dense granular materials display a complicated set of flow properties, which differentiate them from ordinary fluids. Despite their ubiquity, no model has been developed that captures or predicts the complexities of granular flow, posing an obstacle in industrial and geophysical applications. Here we propose a 3D cons...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1219153110

    authors: Henann DL,Kamrin K

    更新日期:2013-04-23 00:00:00

  • Crossover from interaction to driven regimes in quantum vortex reconnections.

    abstract::Reconnections of coherent filamentary structures play a key role in the dynamics of fluids, redistributing energy and helicity among the length scales, triggering dissipative effects, and inducing fine-scale mixing. Unlike ordinary (classical) fluids where vorticity is a continuous field, in superfluid helium and in a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1818668116

    authors: Galantucci L,Baggaley AW,Parker NG,Barenghi CF

    更新日期:2019-06-18 00:00:00

  • Evidence for a biological role in photosynthesis for cytochrome b-559--a component of photosystem II reaction center.

    abstract::Absorbance changes in untreated intact leaf discs, produced upon excitation with high-intensity red light, were shown to be due to the photooxidation of cytochrome b-559. At low intensities (<100 W/m2), photooxidation was almost undetectable. Photooxidation occurred with a half-time of 4.3 sec and an extent of 0.64 mo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.23.9295

    authors: Canaani O,Havaux M

    更新日期:1990-12-01 00:00:00

  • Structure of the human retinoblastoma gene.

    abstract::Complete inactivation of the human retinoblastoma gene (RB) is believed to be an essential step in tumorigenesis of several different cancers. To provide a framework for understanding inactivation mechanisms, the structure of RB was delineated. The RB transcript is encoded in 27 exons dispersed over about 200 kilobase...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.14.5502

    authors: Hong FD,Huang HJ,To H,Young LJ,Oro A,Bookstein R,Lee EY,Lee WH

    更新日期:1989-07-01 00:00:00

  • Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry.

    abstract::We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.131209798

    authors: Hendrix MJ,Seftor EA,Meltzer PS,Gardner LM,Hess AR,Kirschmann DA,Schatteman GC,Seftor RE

    更新日期:2001-07-03 00:00:00

  • Programmable motion of DNA origami mechanisms.

    abstract::DNA origami enables the precise fabrication of nanoscale geometries. We demonstrate an approach to engineer complex and reversible motion of nanoscale DNA origami machine elements. We first design, fabricate, and characterize the mechanical behavior of flexible DNA origami rotational and linear joints that integrate s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1408869112

    authors: Marras AE,Zhou L,Su HJ,Castro CE

    更新日期:2015-01-20 00:00:00

  • Bacteriorhodopsin is involved in halobacterial photoreception.

    abstract::The bacterio-opsin gene was introduced into a "blind" Halobacterium salinarium mutant that (i) lacked all the four retinal proteins [bacteriorhodopsin (BR), halorhodopsin, and sensory rhodopsins (SRs) I and II] and the transducer protein for SRI and (ii) showed neither attractant response to long wavelength light nor ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.20.9446

    authors: Bibikov SI,Grishanin RN,Kaulen AD,Marwan W,Oesterhelt D,Skulachev VP

    更新日期:1993-10-15 00:00:00