当前位置： SCI文献检索 > NATURE期刊下所有文献 > Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Abstract：

:Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy.

journal_name

Nature

journal_title

Nature

authors

Shi Y,Gao W,Lytle NK,Huang P,Yuan X,Dann AM,Ridinger-Saison M,DelGiorno KE,Antal CE,Liang G,Atkins AR,Erikson G,Sun H,Meisenhelder J,Terenziani E,Woo G,Fang L,Santisakultarm TP,Manor U,Xu R,Becerra CR,Borazanci

doi

10.1038/s41586-019-1130-6

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

131-135

issue

7754

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-019-1130-6

journal_volume

569

pub_type

杂志文章

相关文献

NATURE文献大全
  • Transient radio bursts from rotating neutron stars.

    abstract：:The radio sky is relatively unexplored for transient signals, although the potential of radio-transient searches is high. This was demonstrated recently by the discovery of a previously unknown type of source, varying on timescales of minutes to hours. Here we report a search for radio sources that vary on much shorte...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature04440

    authors： McLaughlin MA,Lyne AG,Lorimer DR,Kramer M,Faulkner AJ,Manchester RN,Cordes JM,Camilo F,Possenti A,Stairs IH,Hobbs G,D'Amico N,Burgay M,O'Brien JT

    更新日期：2006-02-16 00:00:00

  • Simple RNA enzymes with new and highly specific endoribonuclease activities.

    abstract：:In vitro mutagenesis of sequences required for the self-catalysed cleavage of a plant virus satellite RNA has allowed definition of an RNA segment with endoribonuclease activity. General rules have been deduced for the design of new RNA enzymes capable of highly specific RNA cleavage, and have been successfully tested...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/334585a0

    authors： Haseloff J,Gerlach WL

    更新日期：1988-08-18 00:00:00

  • Light-inducible and chloroplast-associated expression of a chimaeric gene introduced into Nicotiana tabacum using a Ti plasmid vector.

    abstract：:A chimaeric gene, consisting of the 5'-flanking region of a member of the Pisum sativum gene family encoding ribulose 1,5-bisphosphate carboxylase linked to the coding region of a bacterial chloramphenicol acetyltransferase gene, has been introduced into the genome of the plant Nicotiana tabacum using a Ti plasmid of ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/310115a0

    authors： Herrera-Estrella L,Van den Broeck G,Maenhaut R,Van Montagu M,Schell J,Timko M,Cashmore A

    更新日期：1984-07-12 00:00:00

  • Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle.

    abstract：:In yeast and somatic cells, mechanisms ensure cell-cycle events are initiated only when preceding events have been completed. In contrast, interruption of specific cell-cycle processes in early embryonic cells of many organisms does not affect the timing of subsequent events, indicating that cell-cycle events are trig...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/43927

    authors： Haase SB,Reed SI

    更新日期：1999-09-23 00:00:00

  • Mutations in NOTCH1 cause aortic valve disease.

    abstract：:Calcification of the aortic valve is the third leading cause of heart disease in adults. The incidence increases with age, and it is often associated with a bicuspid aortic valve present in 1-2% of the population. Despite the frequency, neither the mechanisms of valve calcification nor the developmental origin of a tw...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature03940

    authors： Garg V,Muth AN,Ransom JF,Schluterman MK,Barnes R,King IN,Grossfeld PD,Srivastava D

    更新日期：2005-09-08 00:00:00

  • G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2.

    abstract：:Muscarinic receptors of cardiac pacemaker and atrial cells are linked to a potassium channel (IK.ACh) by a pertussis toxin-sensitive GTP-binding protein. The dissociation of G-proteins leads to the generation of two potential transducing elements, alpha-GTP and beta gamma. IK.ACh is activated by G-protein alpha- and b...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/337557a0

    authors： Kim D,Lewis DL,Graziadei L,Neer EJ,Bar-Sagi D,Clapham DE

    更新日期：1989-02-09 00:00:00

  • Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c.

    abstract：:The T-cell receptor is a cell surface heterodimer consisting of an alpha and a beta chain that binds foreign antigen in the context of a cell surface molecule encoded by the major histocompatibility complex (MHC), thus restricting the T-cell response to the surface of antigen presenting cells. The variable (V) domain ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/324679a0

    authors： Winoto A,Urban JL,Lan NC,Goverman J,Hood L,Hansburg D

    更新日期：1986-12-18 00:00:00

  • Inhibition of monoamine oxidase B in the brains of smokers.

    abstract：:The massive health problem associated with cigarette smoking is exacerbated by the addictive properties of tobacco smoke and the limited success of current approaches to cessation of smoking. Yet little is known about the neuropharmacological actions of cigarette smoke that contribute to smoking behaviour, or why smok...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/379733a0

    authors： Fowler JS,Volkow ND,Wang GJ,Pappas N,Logan J,MacGregor R,Alexoff D,Shea C,Schlyer D,Wolf AP,Warner D,Zezulkova I,Cilento R

    更新日期：1996-02-22 00:00:00

  • TMEM16A confers receptor-activated calcium-dependent chloride conductance.

    abstract：:Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remain...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07313

    authors： Yang YD,Cho H,Koo JY,Tak MH,Cho Y,Shim WS,Park SP,Lee J,Lee B,Kim BM,Raouf R,Shin YK,Oh U

    更新日期：2008-10-30 00:00:00

  • Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene.

    abstract：:Haemophilia B (Christmas disease) is an inherited, recessive, sex-linked, haemorrhagic condition caused by a defect in the intrinsic clotting factor IX. This disease occurs in males at a frequency of approximately 1 in 30,000. Patients differ in the severity of their clinical symptoms, and variation in the clotting ac...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/316643a0

    authors： Rees DJ,Rizza CR,Brownlee GG

    更新日期：1985-08-15 00:00:00

  • The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency.

    abstract：:The TGFβ pathway has essential roles in embryonic development, organ homeostasis, tissue repair and disease. These diverse effects are mediated through the intracellular effectors SMAD2 and SMAD3 (hereafter SMAD2/3), whose canonical function is to control the activity of target genes by interacting with transcriptiona...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature25784

    authors： Bertero A,Brown S,Madrigal P,Osnato A,Ortmann D,Yiangou L,Kadiwala J,Hubner NC,de Los Mozos IR,Sadée C,Lenaerts AS,Nakanoh S,Grandy R,Farnell E,Ule J,Stunnenberg HG,Mendjan S,Vallier L

    更新日期：2018-03-08 00:00:00

  • An integrated physical map of human chromosome 16.

    abstract：:We describe an integrated physical, genetic and cytogenetic map of human chromosome 16 comprising both a low-resolution megaYAC map and a high-resolution cosmid contig/miniYAC map, which provides nearly complete coverage of the euchromatic arms of the chromosome. The physical map is anchored to a high-resolution cytog...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/377335a0

    authors： Doggett NA,Goodwin LA,Tesmer JG,Meincke LJ,Bruce DC,Clark LM,Altherr MR,Ford AA,Chi HC,Marrone BL

    更新日期：1995-09-28 00:00:00

  • A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus.

    abstract：:Mice express a collection of superantigens, which bind to class II major histocompatibility proteins and interact with T cells bearing particular V beta chains as part of their alpha beta receptors. These superantigens have been suggested to be encoded by exogenous or endogenous mouse mammary tumour viruses. One such ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/350203a0

    authors： Choi Y,Kappler JW,Marrack P

    更新日期：1991-03-21 00:00:00

  • Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB.

    abstract：:Lantibiotics are a class of peptide antibiotics that contain one or more thioether bonds. The lantibiotic nisin is an antimicrobial peptide that is widely used as a food preservative to combat food-borne pathogens. Nisin contains dehydroalanine and dehydrobutyrine residues that are formed by the dehydration of Ser/Thr...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature13888

    authors： Ortega MA,Hao Y,Zhang Q,Walker MC,van der Donk WA,Nair SK

    更新日期：2015-01-22 00:00:00

  • A supermassive black hole in an ultra-compact dwarf galaxy.

    abstract：:Ultra-compact dwarf galaxies are among the densest stellar systems in the Universe. These systems have masses of up to 2 × 10(8) solar masses, but half-light radii of just 3-50 parsecs. Dynamical mass estimates show that many such dwarfs are more massive than expected from their luminosity. It remains unclear whether ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature13762

    authors： Seth AC,van den Bosch R,Mieske S,Baumgardt H,den Brok M,Strader J,Neumayer N,Chilingarian I,Hilker M,McDermid R,Spitler L,Brodie J,Frank MJ,Walsh JL

    更新日期：2014-09-18 00:00:00

  • Activation of muscle genes without myogenesis by ectopic expression of MyoD in frog embryo cells.

    abstract：:The sequence-specific DNA-binding protein, MyoD, can activate muscle-specific gene expression in some cells in culture. Xenopus MyoD (XMyoD) transcription is activated as a consequence of mesoderm induction in the early myotomes, from which the axial musculature develops. XMyoD RNA accumulates about two hours before m...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/347197a0

    authors： Hopwood ND,Gurdon JB

    更新日期：1990-09-13 00:00:00

  • Characterization of the 1S-2S transition in antihydrogen.

    abstract：:In 1928, Dirac published an equation 1 that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was conf...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/s41586-018-0017-2

    authors： Ahmadi M,Alves BXR,Baker CJ,Bertsche W,Capra A,Carruth C,Cesar CL,Charlton M,Cohen S,Collister R,Eriksson S,Evans A,Evetts N,Fajans J,Friesen T,Fujiwara MC,Gill DR,Hangst JS,Hardy WN,Hayden ME,Isaac CA,Johnson M

    更新日期：2018-05-01 00:00:00

  • Immunology: Insulin auto-antigenicity in type 1 diabetes.

    abstract：:Spontaneous type 1 diabetes occurs when the autoimmune destruction of pancreatic beta-islet cells prevents production of the hormone insulin. This causes an inability to regulate glucose metabolism, which results in dangerously raised blood glucose concentrations. It is generally accepted that thymus-derived lymphocyt...

    journal_title：Nature

    pub_type： 评论,杂志文章

    doi：10.1038/nature04423

    authors： Wilson DB

    更新日期：2005-11-24 00:00:00

  • Cloning, sequence and expression of human interleukin-2 receptor.

    abstract：:T lymphocytes, essential for the generation of a normal immune response, require the presence of the lymphokine interleukin-2 (IL-2) in order to proliferate. Cells that respond to IL-2 possess a surface receptor glycoprotein specific for this lymphokine. We have recently purified and chemically characterized the IL-2 ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/312768a0

    authors： Cosman D,Cerretti DP,Larsen A,Park L,March C,Dower S,Gillis S,Urdal D

    更新日期：1984-12-20 00:00:00

  • Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms.

    abstract：:In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an im...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature25982

    authors： McQuaid JB,Kustka AB,Oborník M,Horák A,McCrow JP,Karas BJ,Zheng H,Kindeberg T,Andersson AJ,Barbeau KA,Allen AE

    更新日期：2018-03-22 00:00:00

  • Human adult germline stem cells in question.

    abstract：:Conrad et al. have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comp...

    journal_title：Nature

    pub_type： 评论,杂志文章

    doi：10.1038/nature09089

    authors： Ko K,Araúzo-Bravo MJ,Tapia N,Kim J,Lin Q,Bernemann C,Han DW,Gentile L,Reinhardt P,Greber B,Schneider RK,Kliesch S,Zenke M,Schöler HR

    更新日期：2010-06-24 00:00:00

  • Imperfect optics may be the eye's defence against chromatic blur.

    abstract：:The optics of the eye cause different wavelengths of light to be differentially focused at the retina. This phenomenon is due to longitudinal chromatic aberration, a wavelength-dependent change in refractive power. Retinal image quality may consequently vary for the different classes of cone photoreceptors, cells tune...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/417174a

    authors： McLellan JS,Marcos S,Prieto PM,Burns SA

    更新日期：2002-05-09 00:00:00

  • Multiple conductance channels in type-2 cerebellar astrocytes activated by excitatory amino acids.

    abstract：:L-GLUTAMATE and L-aspartate are thought to have a widespread function as synaptic transmitters in the mammalian central nervous system and there are at least three types of neuronal glutamate receptors, which can be activated by the selective agonists N-methyl-D-aspartate (NMDA), quisqualate and kainate. Recent experi...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/339380a0

    authors： Usowicz MM,Gallo V,Cull-Candy SG

    更新日期：1989-06-01 00:00:00

  • T-helper-1-cell cytokines drive cancer into senescence.

    abstract：:Cancer control by adaptive immunity involves a number of defined death and clearance mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-γ (IFN-γ) requires additional undefined mechanisms that arrest cancer cell proliferation. Here we show that the combined action of the T-...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature11824

    authors： Braumüller H,Wieder T,Brenner E,Aßmann S,Hahn M,Alkhaled M,Schilbach K,Essmann F,Kneilling M,Griessinger C,Ranta F,Ullrich S,Mocikat R,Braungart K,Mehra T,Fehrenbacher B,Berdel J,Niessner H,Meier F,van den Broek M,

    更新日期：2013-02-21 00:00:00

  • An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis.

    abstract：:Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture. One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbic...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07972

    authors： Cicchillo RM,Zhang H,Blodgett JA,Whitteck JT,Li G,Nair SK,van der Donk WA,Metcalf WW

    更新日期：2009-06-11 00:00:00

  • Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II.

    abstract：:The RNA polymerase II general transcription factor TFIIH is composed of several polypeptides. The observation that the largest subunit of TFIIH is the excision-repair protein XPB/ERCC3 (ref. 1), a helicase implicated in the human DNA-repair disorders xeroderma pigmentosum (XP) and Cockayne's syndrome, suggests a funct...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/368769a0

    authors： Drapkin R,Reardon JT,Ansari A,Huang JC,Zawel L,Ahn K,Sancar A,Reinberg D

    更新日期：1994-04-21 00:00:00

  • Non-equivalent contributions of maternal and paternal genomes to early plant embryogenesis.

    abstract：:Zygotic genome activation in metazoans typically occurs several hours to a day after fertilization, and thus maternal RNAs and proteins drive early animal embryo development. In plants, despite several molecular studies of post-fertilization transcriptional activation, the timing of zygotic genome activation remains a...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature13620

    authors： Del Toro-De León G,García-Aguilar M,Gillmor CS

    更新日期：2014-10-30 00:00:00

  • A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs.

    abstract：:In vertebrates, unfertilized eggs (or mature oocytes) are arrested at metaphase of meiosis II by a cytoplasmic activity called cytostatic factor (CSF). The classical Mos-MAPK pathway has long been implicated in CSF arrest of vertebrate eggs, but exactly how it exerts CSF activity remains unclear. Recently, Erp1 (also ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature05688

    authors： Inoue D,Ohe M,Kanemori Y,Nobui T,Sagata N

    更新日期：2007-04-26 00:00:00

  • Modelling vaccination strategies against foot-and-mouth disease.

    abstract：:Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature01343

    authors： Keeling MJ,Woolhouse ME,May RM,Davies G,Grenfell BT

    更新日期：2003-01-09 00:00:00

  • The genome of Tetranychus urticae reveals herbivorous pest adaptations.

    abstract：:The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the sma...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature10640

    authors： Grbić M,Van Leeuwen T,Clark RM,Rombauts S,Rouzé P,Grbić V,Osborne EJ,Dermauw W,Ngoc PC,Ortego F,Hernández-Crespo P,Diaz I,Martinez M,Navajas M,Sucena É,Magalhães S,Nagy L,Pace RM,Djuranović S,Smagghe G,Iga M,Chr

    更新日期：2011-11-23 00:00:00