A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer.

Abstract:

:Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment.

journal_name

Nat Commun

journal_title

Nature communications

authors

Kodama M,Oshikawa K,Shimizu H,Yoshioka S,Takahashi M,Izumi Y,Bamba T,Tateishi C,Tomonaga T,Matsumoto M,Nakayama KI

doi

10.1038/s41467-020-15136-9

subject

Has Abstract

pub_date

2020-03-17 00:00:00

pages

1320

issue

1

issn

2041-1723

pii

10.1038/s41467-020-15136-9

journal_volume

11

pub_type

杂志文章
  • Evaluating climate geoengineering proposals in the context of the Paris Agreement temperature goals.

    abstract::Current mitigation efforts and existing future commitments are inadequate to accomplish the Paris Agreement temperature goals. In light of this, research and debate are intensifying on the possibilities of additionally employing proposed climate geoengineering technologies, either through atmospheric carbon dioxide re...

    journal_title:Nature communications

    pub_type: 杂志文章,评审

    doi:10.1038/s41467-018-05938-3

    authors: Lawrence MG,Schäfer S,Muri H,Scott V,Oschlies A,Vaughan NE,Boucher O,Schmidt H,Haywood J,Scheffran J

    更新日期:2018-09-13 00:00:00

  • Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)-H bonds with alkynes.

    abstract::Transition metal-catalyzed enantioselective Sonogashira-type oxidative C(sp3)-C(sp) coupling of unactivated C(sp3)-H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C(sp3)-H bond functionalization and the inhibition of readily occurring ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-13705-1

    authors: Zhang ZH,Dong XY,Du XY,Gu QS,Li ZL,Liu XY

    更新日期:2019-12-12 00:00:00

  • Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms.

    abstract::MCR-1 is a lipid A modifying enzyme that confers resistance to the antibiotic colistin. Here, we analyse the impact of MCR-1 expression on E. coli morphology, fitness, competitiveness, immune stimulation and virulence. Increased expression of mcr-1 results in decreased growth rate, cell viability, competitive ability ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02149-0

    authors: Yang Q,Li M,Spiller OB,Andrey DO,Hinchliffe P,Li H,MacLean C,Niumsup P,Powell L,Pritchard M,Papkou A,Shen Y,Portal E,Sands K,Spencer J,Tansawai U,Thomas D,Wang S,Wang Y,Shen J,Walsh T

    更新日期:2017-12-12 00:00:00

  • Marine sequestration of carbon in bacterial metabolites.

    abstract::Linking microbial metabolomics and carbon sequestration in the ocean via refractory organic molecules has been hampered by the chemical complexity of dissolved organic matter (DOM). Here, using bioassay experiments and ultra-high resolution metabolic profiling, we demonstrate that marine bacteria rapidly utilize simpl...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7711

    authors: Lechtenfeld OJ,Hertkorn N,Shen Y,Witt M,Benner R

    更新日期:2015-03-31 00:00:00

  • Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production.

    abstract::Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05387-y

    authors: Amini P,Stojkov D,Felser A,Jackson CB,Courage C,Schaller A,Gelman L,Soriano ME,Nuoffer JM,Scorrano L,Benarafa C,Yousefi S,Simon HU

    更新日期:2018-07-27 00:00:00

  • Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein.

    abstract::Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus-cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural an...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01708-9

    authors: Battles MB,Más V,Olmedillas E,Cano O,Vázquez M,Rodríguez L,Melero JA,McLellan JS

    更新日期:2017-11-16 00:00:00

  • Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a KRAS-specific vulnerability.

    abstract::In human cancers, oncogenic mutations commonly occur in the RAS genes KRAS, NRAS, or HRAS, but there are no clinical RAS inhibitors. Mutations are more prevalent in KRAS, possibly suggesting a unique oncogenic activity mediated by KRAS-specific interaction partners, which might be targeted. Here, we determine the spec...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05692-6

    authors: Adhikari H,Counter CM

    更新日期:2018-09-07 00:00:00

  • Relativistic magnetic reconnection driven by a laser interacting with a micro-scale plasma slab.

    abstract::Magnetic reconnection (MR) is a fundamental plasma process associated with conversion of the magnetic field energy into kinetic plasma energy, which is invoked to explain many non-thermal signatures in astrophysical events. Here we demonstrate that ultrafast relativistic MR in a magnetically dominated regime can be tr...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04065-3

    authors: Yi L,Shen B,Pukhov A,Fülöp T

    更新日期:2018-04-23 00:00:00

  • Decadal predictions of the North Atlantic CO2 uptake.

    abstract::As a major CO2 sink, the North Atlantic, especially its subpolar gyre region, is essential for the global carbon cycle. Decadal fluctuations of CO2 uptake in the North Atlantic subpolar gyre region are associated with the evolution of the North Atlantic Oscillation, the Atlantic meridional overturning circulation, oce...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms11076

    authors: Li H,Ilyina T,Müller WA,Sienz F

    更新日期:2016-03-30 00:00:00

  • Using controlled disorder to probe the interplay between charge order and superconductivity in NbSe2.

    abstract::The interplay between superconductivity and charge-density wave (CDW) in 2H-NbSe2 is not fully understood despite decades of study. Artificially introduced disorder can tip the delicate balance between two competing long-range orders, and reveal the underlying interactions that give rise to them. Here we introduce dis...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05153-0

    authors: Cho K,Kończykowski M,Teknowijoyo S,Tanatar MA,Guss J,Gartin PB,Wilde JM,Kreyssig A,McQueeney RJ,Goldman AI,Mishra V,Hirschfeld PJ,Prozorov R

    更新日期:2018-07-18 00:00:00

  • Near-field interferometry of a free-falling nanoparticle from a point-like source.

    abstract::Matter-wave interferometry performed with massive objects elucidates their wave nature and thus tests the quantum superposition principle at large scales. Whereas standard quantum theory places no limit on particle size, alternative, yet untested theories--conceived to explain the apparent quantum to classical transit...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5788

    authors: Bateman J,Nimmrichter S,Hornberger K,Ulbricht H

    更新日期:2014-09-02 00:00:00

  • Scanning STED-FCS reveals spatiotemporal heterogeneity of lipid interaction in the plasma membrane of living cells.

    abstract::The interaction of lipids and proteins plays an important role in plasma membrane bioactivity, and much can be learned from their diffusion characteristics. Here we present the combination of super-resolution STED microscopy with scanning fluorescence correlation spectroscopy (scanning STED-FCS, sSTED-FCS) to characte...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6412

    authors: Honigmann A,Mueller V,Ta H,Schoenle A,Sezgin E,Hell SW,Eggeling C

    更新日期:2014-11-20 00:00:00

  • Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci.

    abstract::Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly encoding the DNA methylome. Therefore, genetic polymorphism impacts on the observed...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01586-1

    authors: Bell CG,Gao F,Yuan W,Roos L,Acton RJ,Xia Y,Bell J,Ward K,Mangino M,Hysi PG,Wang J,Spector TD

    更新日期:2018-01-02 00:00:00

  • The photospheric origin of the Yonetoku relation in gamma-ray bursts.

    abstract::Long duration gamma-ray bursts (GRBs), the brightest events since the Big Bang itself, are believed to originate in an ultra-relativistic jet breaking out from a massive stellar envelope. Despite decades of study, there is still no consensus on their emission mechanism. One unresolved question is the origin of the tig...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09281-z

    authors: Ito H,Matsumoto J,Nagataki S,Warren DC,Barkov MV,Yonetoku D

    更新日期:2019-04-03 00:00:00

  • Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery.

    abstract::Hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter. This results in the loss of glial cells, significant disruptions in myelination, and thereby cognitive and behavioral disabilities seen throughout life. Encouragingly, these...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14762-7

    authors: Forbes TA,Goldstein EZ,Dupree JL,Jablonska B,Scafidi J,Adams KL,Imamura Y,Hashimoto-Torii K,Gallo V

    更新日期:2020-02-19 00:00:00

  • Lithium lanthanum titanate perovskite as an anode for lithium ion batteries.

    abstract::Conventional lithium-ion batteries embrace graphite anodes which operate at potential as low as metallic lithium, subjected to poor rate capability and safety issues. Among possible alternatives, oxides based on titanium redox couple, such as spinel Li4Ti5O12, have received renewed attention. Here we further expand th...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17233-1

    authors: Zhang L,Zhang X,Tian G,Zhang Q,Knapp M,Ehrenberg H,Chen G,Shen Z,Yang G,Gu L,Du F

    更新日期:2020-07-13 00:00:00

  • Complex formation of APP with GABAB receptors links axonal trafficking to amyloidogenic processing.

    abstract::GABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three in...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09164-3

    authors: Dinamarca MC,Raveh A,Schneider A,Fritzius T,Früh S,Rem PD,Stawarski M,Lalanne T,Turecek R,Choo M,Besseyrias V,Bildl W,Bentrop D,Staufenbiel M,Gassmann M,Fakler B,Schwenk J,Bettler B

    更新日期:2019-03-22 00:00:00

  • Electrochemically tunable thermal conductivity of lithium cobalt oxide.

    abstract::Using time-domain thermoreflectance, the thermal conductivity and elastic properties of a sputter deposited LiCoO2 film, a common lithium-ion cathode material, are measured as a function of the degree of lithiation. Here we report that via in situ measurements during cycling, the thermal conductivity of a LiCoO2 catho...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms5035

    authors: Cho J,Losego MD,Zhang HG,Kim H,Zuo J,Petrov I,Cahill DG,Braun PV

    更新日期:2014-06-03 00:00:00

  • Experimental protocol for high-fidelity heralded photon-to-atom quantum state transfer.

    abstract::A quantum network combines the benefits of quantum systems regarding secure information transmission and calculational speed-up by employing quantum coherence and entanglement to store, transmit and process information. A promising platform for implementing such a network are atom-based quantum memories and processors...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms6527

    authors: Kurz C,Schug M,Eich P,Huwer J,Müller P,Eschner J

    更新日期:2014-11-21 00:00:00

  • The footprint of column collapse regimes on pyroclastic flow temperatures and plume heights.

    abstract::The gravitational collapse of eruption columns generates ground-hugging pyroclastic density currents (PDCs) with highly variable temperatures, high enough to be a threat for communities surrounding volcanoes. The reasons for such great temperature variability are debated in terms of eruptive versus transport and empla...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-10337-3

    authors: Trolese M,Cerminara M,Esposti Ongaro T,Giordano G

    更新日期:2019-06-06 00:00:00

  • Large spatial extension of the zero-energy Yu-Shiba-Rusinov state in a magnetic field.

    abstract::Various promising qubit concepts have been put forward recently based on engineered superconductor subgap states like Andreev bound states, Majorana zero modes or the Yu-Shiba-Rusinov (Shiba) states. The coupling of these subgap states via a superconductor strongly depends on their spatial extension and is an essentia...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15322-9

    authors: Scherübl Z,Fülöp G,Moca CP,Gramich J,Baumgartner A,Makk P,Elalaily T,Schönenberger C,Nygård J,Zaránd G,Csonka S

    更新日期:2020-04-14 00:00:00

  • A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay.

    abstract::Nonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms15943

    authors: Hu Z,Yau C,Ahmed AA

    更新日期:2017-06-26 00:00:00

  • MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.

    abstract::MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 i...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14270

    authors: Liu C,Liu R,Zhang D,Deng Q,Liu B,Chao HP,Rycaj K,Takata Y,Lin K,Lu Y,Zhong Y,Krolewski J,Shen J,Tang DG

    更新日期:2017-01-23 00:00:00

  • Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.

    abstract::Frameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels are degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17526-5

    authors: Litchfield K,Reading JL,Lim EL,Xu H,Liu P,Al-Bakir M,Wong YNS,Rowan A,Funt SA,Merghoub T,Perkins D,Lauss M,Svane IM,Jönsson G,Herrero J,Larkin J,Quezada SA,Hellmann MD,Turajlic S,Swanton C

    更新日期:2020-07-30 00:00:00

  • Stratospheric ozone loss over the Eurasian continent induced by the polar vortex shift.

    abstract::The Montreal Protocol has succeeded in limiting major ozone-depleting substance emissions, and consequently stratospheric ozone concentrations are expected to recover this century. However, there is a large uncertainty in the rate of regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia-North ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-02565-2

    authors: Zhang J,Tian W,Xie F,Chipperfield MP,Feng W,Son SW,Abraham NL,Archibald AT,Bekki S,Butchart N,Deushi M,Dhomse S,Han Y,Jöckel P,Kinnison D,Kirner O,Michou M,Morgenstern O,O'Connor FM,Pitari G,Plummer DA,Revell LE

    更新日期:2018-01-15 00:00:00

  • Spin transport and Hanle effect in silicon nanowires using graphene tunnel barriers.

    abstract::Spin-based devices offer non-volatile, scalable, low power and reprogrammable functionality for emerging device technologies. Here we fabricate nanoscale spintronic devices with ferromagnetic metal/single-layer graphene tunnel barriers used to generate spin accumulation and spin currents in a silicon nanowire transpor...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8541

    authors: van 't Erve OM,Friedman AL,Li CH,Robinson JT,Connell J,Lauhon LJ,Jonker BT

    更新日期:2015-06-19 00:00:00

  • A metallic molybdenum dioxide with high stability for surface enhanced Raman spectroscopy.

    abstract::Compared with noble metals, semiconductors with surface plasmon resonance effect are another type of SERS substrate materials. The main obstacles so far are that the semiconducting materials are often unstable and easy to be further oxidized or decomposed by laser irradiating or contacting with corrosive substances. H...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14903

    authors: Zhang Q,Li X,Ma Q,Zhang Q,Bai H,Yi W,Liu J,Han J,Xi G

    更新日期:2017-04-24 00:00:00

  • Oscillatory integration windows in neurons.

    abstract::Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13808

    authors: Gupta N,Singh SS,Stopfer M

    更新日期:2016-12-15 00:00:00

  • Elastic spheres can walk on water.

    abstract::Incited by public fascination and engineering application, water-skipping of rigid stones and spheres has received considerable study. While these objects can be coaxed to ricochet, elastic spheres demonstrate superior water-skipping ability, but little is known about the effect of large material compliance on water i...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10551

    authors: Belden J,Hurd RC,Jandron MA,Bower AF,Truscott TT

    更新日期:2016-02-04 00:00:00

  • Interactions between Twist and other core epithelial-mesenchymal transition factors are controlled by GSK3-mediated phosphorylation.

    abstract::A subset of transcription factors classified as neural crest 'specifiers' are also core epithelial-mesenchymal transition regulatory factors, both in the neural crest and in tumour progression. The bHLH factor Twist is among the least well studied of these factors. Here we demonstrate that Twist is required for crania...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms2543

    authors: Lander R,Nasr T,Ochoa SD,Nordin K,Prasad MS,Labonne C

    更新日期:2013-01-01 00:00:00