Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells.

Abstract:

:Loss or reduction in function of tumor suppressor genes contributes to tumorigenesis. Here, by allelic DNA copy number analysis using single-nucleotide polymorphism genotyping array and mass spectrometry, we report homozygous deletion in glioblastoma multiformes at chromosome 13q21, where DACH1 gene is located. We found decreased cell proliferation of a series of glioma cell lines by forced expression of DACH1. We then generated U87TR-Da glioma cells, where DACH1 expression could be activated by exposure of the cells to doxycycline. Both ex vivo cellular proliferation and in vivo growth of s.c. transplanted tumors in mice are reduced in U87TR-Da cells with DACH1 expression (U87-DACH1-high), compared with DACH1-nonexpressing U87TR-Da cells (U87-DACH1-low). U87-DACH1-low cells form spheroids with CD133 and Nestin expression in serum-free medium but U87-DACH1-high cells do not. Compared with spheroid-forming U87-DACH1-low cells, adherent U87-DACH1-high cells display lower tumorigenicity, indicating DACH1 decreases the number of tumor-initiating cells. Gene expression analysis and chromatin immunoprecipitation assay reveal that fibroblast growth factor 2 (FGF2/bFGF) is transcriptionally repressed by DACH1, especially in cells cultured in serum-free medium. Exogenous bFGF rescues spheroid-forming activity and tumorigenicity of the U87-DACH1-high cells, suggesting that loss of DACH1 increases the number of tumor-initiating cells through transcriptional activation of bFGF. These results illustrate that DACH1 is a distinctive tumor suppressor, which does not only suppress growth of tumor cells but also regulates bFGF-mediated tumor-initiating activity of glioma cells.

authors

Watanabe A,Ogiwara H,Ehata S,Mukasa A,Ishikawa S,Maeda D,Ueki K,Ino Y,Todo T,Yamada Y,Fukayama M,Saito N,Miyazono K,Aburatani H

doi

10.1073/pnas.0906930108

subject

Has Abstract

pub_date

2011-07-26 00:00:00

pages

12384-9

issue

30

eissn

0027-8424

issn

1091-6490

pii

0906930108

journal_volume

108

pub_type

杂志文章
  • Constitutive activity of the tumor necrosis factor promoter is canceled by the 3' untranslated region in nonmacrophage cell lines; a trans-dominant factor overcomes this suppressive effect.

    abstract::The role of the mouse tumor necrosis factor (TNF) promoter, 5' untranslated region (UTR), and 3' UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in ...

    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.89.2.673

    authors: Kruys V,Kemmer K,Shakhov A,Jongeneel V,Beutler B

    更新日期:1992-01-15 00:00:00

  • The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

    abstract::Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of ph...

    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.1403667112

    authors: Goswami A,Binder WJ,Meachen J,O'Keefe FR

    更新日期:2015-04-21 00:00:00

  • Habituation as a neural algorithm for online odor discrimination.

    abstract::Habituation is a form of simple memory that suppresses neural activity in response to repeated, neutral stimuli. This process is critical in helping organisms guide attention toward the most salient and novel features in the environment. Here, we follow known circuit mechanisms in the fruit fly olfactory system to der...

    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.1915252117

    authors: Shen Y,Dasgupta S,Navlakha S

    更新日期:2020-06-02 00:00:00

  • Expression cloning of rat renal Na+/SO4(2-) cotransport.

    abstract::Injection of rat kidney cortex mRNA into Xenopus laevis oocytes leads to a stimulation of Na(+)-dependent SO4(2-) uptake. Based on this information, we have isolated from a corresponding library a cDNA (NaSi-1) that is most likely related to a Na+/SO4(2-) cotransport system. NaSi-1 cRNA leads in a time- and dose-depen...

    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.90.17.8073

    authors: Markovich D,Forgo J,Stange G,Biber J,Murer H

    更新日期:1993-09-01 00:00:00

  • Reciprocity and behavioral heterogeneity govern the stability of social networks.

    abstract::The dynamics of social networks can determine the transmission of information, the spread of diseases, and the evolution of behavior. Despite this broad importance, a general framework for predicting social network stability has not been proposed. Here we present longitudinal data on the social dynamics of a cooperati...

    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.1913284117

    authors: Dakin R,Ryder TB

    更新日期:2020-02-11 00:00:00

  • A putative ATP-dependent RNA helicase involved in Saccharomyces cerevisiae ribosome assembly.

    abstract::We have isolated a cold-sensitive mutant of Saccharomyces cerevisiae in which there is a deficit of 60S ribosomal subunits. Cold sensitivity and the assembly defect are recessive and cosegregate, defining a single essential gene that we designated DRS1 (deficiency of ribosomal subunits). The wild-type DRS1 gene was cl...

    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.89.23.11131

    authors: Ripmaster TL,Vaughn GP,Woolford JL Jr

    更新日期:1992-12-01 00:00:00

  • Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a.

    abstract::During organogenesis, the final size of mature cell populations depends on their rates of differentiation and expansion. Because transient expression of Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates their differentiation to mature islet cells, we examined the role of Neurog3 in cell cy...

    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.1004842108

    authors: Miyatsuka T,Kosaka Y,Kim H,German MS

    更新日期:2011-01-04 00:00:00

  • Detection of genes with a potential for suppressing the transformed phenotype associated with activated ras genes.

    abstract::Seven morphologically nontransformed (flat) revertants with reduced tumorigenicity in vivo have been isolated from populations of Kirsten sarcoma virus-transformed NIH 3T3 cells transfected with a cDNA expression library of normal human fibroblasts. Each revertant harbors 1-10 recombinant plasmids per cell and retains...

    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.86.1.162

    authors: Noda M,Kitayama H,Matsuzaki T,Sugimoto Y,Okayama H,Bassin RH,Ikawa Y

    更新日期:1989-01-01 00:00:00

  • Expansion of human NK-22 cells with IL-7, IL-2, and IL-1beta reveals intrinsic functional plasticity.

    abstract::Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the survival of NK-22 cells and IL-22 production in response to IL...

    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.1005641107

    authors: Cella M,Otero K,Colonna M

    更新日期:2010-06-15 00:00:00

  • Structural characterization of the D290V mutation site in hnRNPA2 low-complexity-domain polymers.

    abstract::Human genetic studies have given evidence of familial, disease-causing mutations in the analogous amino acid residue shared by three related RNA binding proteins causative of three neurological diseases. Alteration of aspartic acid residue 290 of hnRNPA2 to valine is believed to predispose patients to multisystem prot...

    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.1806174115

    authors: Murray DT,Zhou X,Kato M,Xiang S,Tycko R,McKnight SL

    更新日期:2018-10-16 00:00:00

  • Reconstructing orogens without biostratigraphy: The Saharides and continental growth during the final assembly of Gondwana-Land.

    abstract::A hitherto unknown Neoproterozoic orogenic system, the Saharides, is described in North Africa. It formed during the 900-500-Ma interval. The Saharides involved large subduction accretion complexes occupying almost the entire Arabian Shield and much of Egypt and parts of the small Precambrian inliers in the Sahara inc...

    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.2015117117

    authors: Şengör AMC,Lom N,Zabcı C,Sunal G,Öner T

    更新日期:2020-12-22 00:00:00

  • Scanning tunneling microscopy experiments on single molecular landers.

    abstract::Molecular landers are molecules comprising of a central rigid molecular wire maintained above a metallic surface by organic spacers, which allows specific ultrahigh vacuum-scanning tunneling microscopy experiments to be performed at the single-molecule level. The understanding of the molecule-surface interactions, int...

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

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.0500915102

    authors: Moresco F,Gourdon A

    更新日期:2005-06-21 00:00:00

  • Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy.

    abstract::Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy (ICMP) show a reduced neovascularization capacity in vivo. NO plays an important role in neovascularization, and NO bioavailability is typically reduced in patients with ICMP. We investigated whether the impaired neovascularization capacity...

    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.0604144103

    authors: Sasaki K,Heeschen C,Aicher A,Ziebart T,Honold J,Urbich C,Rossig L,Koehl U,Koyanagi M,Mohamed A,Brandes RP,Martin H,Zeiher AM,Dimmeler S

    更新日期:2006-09-26 00:00:00

  • Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum.

    abstract::The endoplasmic reticulum (ER) plays an important role in peroxisome biogenesis; some peroxisomal membrane proteins are inserted into the ER and trafficked to peroxisomes in vesicles. These vesicles could also provide the phospholipids required for the growth of peroxisomal membranes, because peroxisomes lack phosphol...

    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.0808321105

    authors: Raychaudhuri S,Prinz WA

    更新日期:2008-10-14 00:00:00

  • Origin of nanomechanical cantilever motion generated from biomolecular interactions.

    abstract::Generation of nanomechanical cantilever motion from biomolecular interactions can have wide applications, ranging from high-throughput biomolecular detection to bioactuation. Although it has been suggested that such motion is caused by changes in surface stress of a cantilever beam, the origin of the surface-stress ch...

    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.031362498

    authors: Wu G,Ji H,Hansen K,Thundat T,Datar R,Cote R,Hagan MF,Chakraborty AK,Majumdar A

    更新日期:2001-02-13 00:00:00

  • Neuron densities vary across and within cortical areas in primates.

    abstract::The numbers and proportion of neurons in areas and regions of cortex were determined for a single cortical hemisphere from two prosimian galagos, one New World owl monkey, one Old World macaque monkey, and one baboon. The results suggest that there is a common plan of cortical organization across the species examined ...

    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.1010356107

    authors: Collins CE,Airey DC,Young NA,Leitch DB,Kaas JH

    更新日期:2010-09-07 00:00:00

  • Structure of columns in monkey striate cortex induced by luminant-contrast and color-contrast stimulation.

    abstract::Color and black and white line stimulation produce qualitatively and quantitatively different 2-deoxy[14C]glucose column patterns in the striate cortex of macaque monkeys. Microdensitometry of these stimulus-dependent columns reveals interlaminar density differences that serve as a signature for the stimulus condition...

    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.79.21.6722

    authors: Crawford ML,Meharg LS,Johnston DA

    更新日期:1982-11-01 00:00:00

  • COVID-19 lockdown induces disease-mitigating structural changes in mobility networks.

    abstract::In the wake of the COVID-19 pandemic many countries implemented containment measures to reduce disease transmission. Studies using digital data sources show that the mobility of individuals was effectively reduced in multiple countries. However, it remains unclear whether these reductions caused deeper structural chan...

    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.2012326117

    authors: Schlosser F,Maier BF,Jack O,Hinrichs D,Zachariae A,Brockmann D

    更新日期:2020-12-29 00:00:00

  • A preference for own-subspecies' song guides vocal learning in a song bird.

    abstract::In many song birds, males develop their songs as adults by imitating the songs of one or more tutors, memorized previously during a sensitive phase early in life. Previous work using two assays, the production of imitations by adult males and playback-induced calling by young birds during the sensitive phase for memor...

    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.240457797

    authors: Nelson DA

    更新日期:2000-11-21 00:00:00

  • In vitro evidence that covalent crosslinking of neurofilaments occurs in gamma-diketone neuropathy.

    abstract::We have postulated that the toxic neuropathies associated with neurofilament-filled axonal swellings have a common pathogenesis, the covalent crosslinking of neurofilaments during anterograde transport. The newly described gamma-diketone, 3,4-dimethyl-2,5-hexanedione (DMHD), is a more potent analogue of the toxic meta...

    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.81.15.4979

    authors: Graham DG,Szakál-Quin G,Priest JW,Anthony DC

    更新日期:1984-08-01 00:00:00

  • Protein kinase LKB1 regulates polarized dendrite formation of adult hippocampal newborn neurons.

    abstract::Adult-born granule cells in the dentate gyrus of the rodent hippocampus are important for memory formation and mood regulation, but the cellular mechanism underlying their polarized development, a process critical for their incorporation into functional circuits, remains unknown. We found that deletion of the serine-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.1321454111

    authors: Huang W,She L,Chang XY,Yang RR,Wang L,Ji HB,Jiao JW,Poo MM

    更新日期:2014-01-07 00:00:00

  • Methionine sulfoxide reductase A is a stereospecific methionine oxidase.

    abstract::Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of me...

    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.1101275108

    authors: Lim JC,You Z,Kim G,Levine RL

    更新日期:2011-06-28 00:00:00

  • Amphibian development in the virtual absence of gravity.

    abstract::To test whether gravity is required for normal amphibian development, Xenopus laevis females were induced to ovulate aboard the orbiting Space Shuttle. Eggs were fertilized in vitro, and although early embryonic stages showed some abnormalities, the embryos were able to regulate and produce nearly normal larvae. These...

    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.92.6.1975

    authors: Souza KA,Black SD,Wassersug RJ

    更新日期:1995-03-14 00:00:00

  • Companies' contribution to sustainability through global supply chains.

    abstract::Global supply chains play a critical role in many of the most pressing environmental stresses and social struggles identified by the United Nations' Sustainable Development Goals (SDGs). Responding to calls from the global community, companies are adopting a variety of voluntary practices to improve the environmental ...

    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.1716695115

    authors: Thorlakson T,de Zegher JF,Lambin EF

    更新日期:2018-02-27 00:00:00

  • CO2 reduction driven by a pH gradient.

    abstract::All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, f...

    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.2002659117

    authors: Hudson R,de Graaf R,Strandoo Rodin M,Ohno A,Lane N,McGlynn SE,Yamada YMA,Nakamura R,Barge LM,Braun D,Sojo V

    更新日期:2020-09-15 00:00:00

  • The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.

    abstract::KRAS interacts with the inner leaflet of the plasma membrane (PM) using a hybrid anchor that comprises a lysine-rich polybasic domain (PBD) and a C-terminal farnesyl chain. Electrostatic interactions have been envisaged as the primary determinant of interactions between KRAS and membranes. Here, we integrated molecula...

    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.2014605118

    authors: Zhou Y,Prakash PS,Liang H,Gorfe AA,Hancock JF

    更新日期:2021-02-09 00:00:00

  • Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

    abstract::Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen...

    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.2021450118

    authors: Qiao Y,Wang XM,Mannan R,Pitchiaya S,Zhang Y,Wotring JW,Xiao L,Robinson DR,Wu YM,Tien JC,Cao X,Simko SA,Apel IJ,Bawa P,Kregel S,Narayanan SP,Raskind G,Ellison SJ,Parolia A,Zelenka-Wang S,McMurry L,Su F,Wang R,

    更新日期:2020-12-11 00:00:00

  • Induction of DNA synthesis in terminally differentiated myotubes by the activation of the src gene of Rous sarcoma virus.

    abstract::Mononucleated myogenic cells from 11-day-old chicken embryos were infected with tsLA24 or tsNY68, temperature-sensitive transformation mutants of Rous sarcoma virus. The infected mononucleated myogenic cells were incubated at the nonpermissive temperature (41 degrees C) and allowed to develop into multinucleated myotu...

    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.75.11.5501

    authors: Kobayashi N,Kaji A

    更新日期:1978-11-01 00:00:00

  • Roles of calcium, serum, plasma, and folic acid in the control of proliferation of normal and Rous sarcoma virus-infected chicken fibroblasts.

    abstract::In a culture medium of pH 7.4 and a folic acid concentration of 100 mug/liter that contains 5% heat-inactivated chicken plasma rather than serum, the rate of proliferation of normal chicken fibroblasts is determined by the concentration of calcium. Proliferation, rapid when the calcium concentration is physiological, ...

    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.70.3.675

    authors: Balk SD,Whitfield JF,Youdale T,Braun AC

    更新日期:1973-03-01 00:00:00

  • DNA relaxation dynamics as a probe for the intracellular environment.

    abstract::Investigations into the biophysical properties of single molecules traditionally involve well defined in vitro systems where parameters such as solvent viscosity and applied forces are known a priori. These systems provide means to develop models describing the polymers response to a variety of conditions, including 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.0812723106

    authors: Fisher JK,Ballenger M,O'Brien ET,Haase J,Superfine R,Bloom K

    更新日期:2009-06-09 00:00:00