Abstract:
:KRAS mutations are present in over 90% of pancreatic ductal adenocarcinomas (PDAC), and drive their poor outcomes and failure to respond to targeted therapies. Here we show that Leukemia Inhibitory Factor (LIF) expression is induced specifically by oncogenic KRAS in PDAC and that LIF depletion by genetic means or by neutralizing antibodies prevents engraftment in pancreatic xenograft models. Moreover, LIF-neutralizing antibodies synergize with gemcitabine to eradicate established pancreatic tumors in a syngeneic, KrasG12D-driven, PDAC mouse model. The related cytokine IL-6 cannot substitute for LIF, suggesting that LIF mediates KRAS-driven malignancies through a non-STAT-signaling pathway. Unlike IL-6, LIF inhibits the activity of the Hippo-signaling pathway in PDACs. Depletion of YAP inhibits the function of LIF in human PDAC cells. Our data suggest a crucial role of LIF in KRAS-driven pancreatic cancer and that blockade of LIF by neutralizing antibodies represents an attractive approach to improving therapeutic outcomes.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Wang MT,Fer N,Galeas J,Collisson EA,Kim SE,Sharib J,McCormick Fdoi
10.1038/s41467-019-11044-9subject
Has Abstractpub_date
2019-07-11 00:00:00pages
3055issue
1issn
2041-1723pii
10.1038/s41467-019-11044-9journal_volume
10pub_type
杂志文章abstract::Molecularly targeted therapies for advanced prostate cancer include castration modalities that suppress ligand-dependent transcriptional activity of the androgen receptor (AR). However, persistent AR signalling undermines therapeutic efficacy and promotes progression to lethal castration-resistant prostate cancer (CRP...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13668
更新日期:2016-11-29 00:00:00
abstract::Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. Here we show that MPB is strongly heritable and polygenic, with pedigree-heritability of 0.62 (SE = 0.03) estimated from close relatives, and SNP-heritability of 0.39 (SE = 0.0...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07862-y
更新日期:2018-12-20 00:00:00
abstract::The original version of this Article contained an error in the spelling of the author Jianyun Yan, which was incorrectly given as Jiangyun Yan. This has now been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-017-02617-7
更新日期:2018-01-12 00:00:00
abstract::Membrane transporters actively translocate their substrate by undergoing large-scale structural transitions between inward- (IF) and outward-facing (OF) states ('alternating-access' mechanism). Despite extensive structural studies, atomic-level mechanistic details of such structural transitions, and as importantly, th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9393
更新日期:2015-09-29 00:00:00
abstract::It is evident that epigenetic factors, especially DNA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DNA methylation and obesity. We sample eight variant adipose and two distinct ske...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1854
更新日期:2012-05-22 00:00:00
abstract::Pentacyclic triterpenoids (PTs) constitute one of the biggest families of natural products, many with higher oxidation state at the D/E rings possess a wide spectrum of biological activties but are poorly accessible. Here we report a site-selective C-H hydroxylation at the D/E rings of PTs paving a way toward these im...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18138-9
更新日期:2020-09-01 00:00:00
abstract::Long-range chromosomal interactions bring distal regulatory elements and promoters together to regulate gene expression in biological processes. By performing promoter capture Hi-C (PCHi-C) on human embryonic stem cell-derived cardiomyocytes (hESC-CMs), we show that such promoter interactions are a key mechanism by wh...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-04931-0
更新日期:2018-06-28 00:00:00
abstract::It is generally assumed that cells interrogate the mechanical properties of their environment by pushing and pulling on the extracellular matrix (ECM). For instance, acto-myosin-dependent contraction forces exerted at focal adhesions (FAs) allow the cell to actively probe substrate elasticity. Here, we report that a s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-06367-y
更新日期:2018-09-20 00:00:00
abstract::The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17197-2
更新日期:2020-09-02 00:00:00
abstract::Thin-film transistor (TFT)-driven full-color organic light-emitting diodes (OLEDs) with vertically stacked structures are developed herein using photolithography processes, which allow for high-resolution displays of over 2,000 pixels per inch. Vertical stacking of OLEDs by the photolithography process is technically ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16551-8
更新日期:2020-06-01 00:00:00
abstract::The clockwork of plant circadian oscillators has been resolved through investigations in Arabidopsis thaliana. The circadian oscillator is an important regulator of much of plant physiology, though many of the mechanisms are unclear. New findings demonstrate that the oscillator adjusts phase and period in response to ...
journal_title:Nature communications
pub_type: 杂志文章,评审
doi:10.1038/s41467-019-08398-5
更新日期:2019-02-01 00:00:00
abstract::PIWI-interacting RNAs (piRNAs) are effectors of transposable element (TE) silencing in the reproductive apparatus. In Drosophila ovarian somatic cells, piRNAs arise from longer single-stranded RNA precursors that are processed in the cytoplasm presumably within the Yb-bodies. piRNA precursors encoded by the flamenco (...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13739
更新日期:2016-12-08 00:00:00
abstract::Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bioengineered neural tissue growing in a t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4997
更新日期:2014-06-05 00:00:00
abstract::A planar slab of negative-index material works as a superlens with sub-diffraction-limited resolution, as propagating waves are focused and, moreover, evanescent waves are reconstructed in the image plane. Here we demonstrate a superlens for electric evanescent fields with low losses using perovskites in the mid-infra...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1249
更新日期:2011-01-01 00:00:00
abstract::Yeast lacks dedicated photoreceptors; however, blue light still causes pronounced oscillations of the transcription factor Msn2 into and out of the nucleus. Here we show that this poorly understood phenomenon is initiated by a peroxisomal oxidase, which converts light into a hydrogen peroxide (H2O2) signal that is sen...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms14791
更新日期:2017-03-24 00:00:00
abstract::Recently, stretchable electronics combined with wireless technology have been crucial for realizing efficient human-machine interaction. Here, we demonstrate highly stretchable transparent wireless electronics composed of Ag nanofibers coils and functional electronic components for power transfer and information commu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19367-8
更新日期:2020-11-06 00:00:00
abstract::FBXW2 inhibits proliferation of lung cancer cells by targeting SKP2 for degradation. Whether and how FBXW2 regulates tumor invasion and metastasis is previously unknown. Here, we report that FBXW2 is an E3 ligase for β-catenin. FBXW2 binds to β-catenin upon EGF-AKT1-mediated phosphorylation on Ser552, and promotes its...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09289-5
更新日期:2019-03-27 00:00:00
abstract::Despite progress in understanding pollination network structure, the functional roles of floral sensory stimuli (visual, olfactory) have never been addressed comprehensively in a community context, even though such traits are known to mediate plant-pollinator interactions. Here, we use a comprehensive dataset of flora...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03448-w
更新日期:2018-03-12 00:00:00
abstract::In silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesize that matrices created using only healthy samples from a single microarray platform would introduce biological and technical biases in deconvoluti...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07242-6
更新日期:2018-11-09 00:00:00
abstract::Chirality is an intriguing property of certain molecules, materials or artificial nanostructures, which allows them to interact with the spin angular momentum of the impinging light field. Due to their chiral geometry, they can distinguish between left- and right-hand circular polarization states or convert them into ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13117
更新日期:2016-10-13 00:00:00
abstract::Flexible barrier films preventing permeation of gases and moistures are important for many industries ranging from food to medical and from chemical to electronic. From this perspective, graphene has recently attracted particular interest because its defect-free monolayers are impermeable to all atoms and molecules. H...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5843
更新日期:2014-09-11 00:00:00
abstract::The genome of the thermophilic bacterium, Aeribacillus pallidus 8, encodes the bacteriocin pallidocin. It belongs to the small class of glycocins and is posttranslationally modified, containing an S-linked glucose on a specific Cys residue. In this study, the pallidocin biosynthetic machinery is cloned and expressed i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09065-5
更新日期:2019-03-07 00:00:00
abstract::Electrospun nanofibres are promising in biomedical applications to replicate features of the natural extracellular matrix (ECM). However, nearly all electrospun scaffolds are either non-degradable or degrade hydrolytically, whereas natural ECM degrades proteolytically, often through matrix metalloproteinases. Here we ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7639
更新日期:2015-03-23 00:00:00
abstract::Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes c...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18208-y
更新日期:2020-08-28 00:00:00
abstract::Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12417
更新日期:2016-08-22 00:00:00
abstract::Seeded propagation of amyloid-beta (Aβ) pathology is suggested to contribute to the progression of Alzheimer's disease. Local overproduction of aggregation-prone Aβ variants could explain the focal initiation of a seeding cascade that subsequently triggers widespread pathology. Several animal models support this seedi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00579-4
更新日期:2017-09-11 00:00:00
abstract::The continued convergence of electronics and photonics on the chip scale can benefit from the voltage control of optical polarization for applications in communications, signal processing and sensing. It is challenging, however, to electrically manipulate the polarization state of light in planar optical waveguides. H...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6337
更新日期:2014-11-12 00:00:00
abstract::Transcription preinitiation complex assembly on the promoters of protein encoding genes is nucleated in vivo by TFIID composed of the TATA-box Binding Protein (TBP) and 13 TBP-associate factors (Tafs) providing regulatory and chromatin binding functions. Here we present the cryo-electron microscopy structure of promot...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07096-y
更新日期:2018-11-07 00:00:00
abstract::Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular phase separation have the potential to drive the development of novel liquid-based organelles an...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18224-y
更新日期:2020-09-15 00:00:00
abstract::Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate gr...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4817
更新日期:2014-05-23 00:00:00