Abstract：
:Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer cells express protocadherin 7 (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and tumour necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis.
journal_name
Naturejournal_title
Natureauthors
Chen Q,Boire A,Jin X,Valiente M,Er EE,Lopez-Soto A,Jacob L,Patwa R,Shah H,Xu K,Cross JR,Massagué Jdoi
10.1038/nature18268subject
Has Abstractpub_date
2016-05-26 00:00:00pages
493-498issue
7604eissn
0028-0836issn
1476-4687journal_volume
533pub_type
杂志文章相关文献
NATURE文献大全abstract：:Sex roles are typically thought of as being fixed for a given species. In most animals males compete for females, whereas the females are more reluctant to mate. Therefore sexual selection usually acts most strongly on males. This is explained by males having a higher potential reproductive rate than females, leading ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02562
更新日期：2004-06-03 00:00:00
abstract：:Rheumatoid arthritis is a chronic autoinflammatory disease that affects 1-2% of the world's population and is characterized by widespread joint inflammation. Interleukin-1 is an important mediator of cartilage destruction in rheumatic diseases, but our understanding of the upstream mechanisms leading to production of ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13322
更新日期：2014-08-07 00:00:00
abstract：:A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer c...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature06487
更新日期：2008-01-10 00:00:00
abstract：:Large mammals, including humans, save much of the energy needed for running by means of elastic structures in their legs and feet. Kinetic and potential energy removed from the body in the first half of the stance phase is stored briefly as elastic strain energy and then returned in the second half by elastic recoil. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/325147a0
更新日期：1987-01-08 00:00:00
abstract：:Receptors for excitatory amino acids in the mammalian central nervous system are classified into three major subtypes, ones which prefer N-methyl-D-aspartate (NMDA), quisqualate (QA), or kainate (KA) as type agonists respectively. These receptors are considered to mediate fast postsynaptic potentials by activating ion...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/325531a0
更新日期：1987-02-05 00:00:00
abstract：:Inhibin is a hypophysiotropic hormone which selectively suppresses the secretion of pituitary follicle-stimulating hormone. It has been isolated from gonadal fluids and characterized as a protein heterodimer consisting of an alpha subunit and one of two beta subunits (beta A or beta B). FSH-releasing protein (FRP), al...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/330765a0
更新日期：1987-12-24 00:00:00
abstract：:Ligand-gated ion channels are multi-subunit complexes where each subunit-type is encoded by several related genes. Heterologous expression of any one of the neuronal nicotinic acetylcholine receptors (nAChR) alpha-type subunits, either alone or with any beta-type subunit, typically yields functional nAChR channels. A ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/380347a0
更新日期：1996-03-28 00:00:00
abstract：:The human T-cell leukaemia and differentiation antigen HTA 1 is defined by the monoclonal antibody NA1/34 (ref. 1) and also recognized by the monoclonal antibody OKT6. Like class I products of the human major histocompatibility complex, it has a glycosylated heavy (alpha) chain of approximately 45-50,000 molecular wei...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/308641a0
更新日期：1984-04-12 00:00:00
abstract：:The bmi-1 proto-oncogene can be activated by Moloney murine leukaemia proviral insertions in E mu-myc transgenic mice. It encodes a highly conserved nuclear protein of 324 amino acids which belongs to a family of proteins containing a putative new zinc-finger. Another closely related member of this family is the mouse...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/353353a0
更新日期：1991-09-26 00:00:00
abstract：:The evolutionary theory of ageing explains why ageing occurs, giving valuable insight into the mechanisms underlying the complex cellular and molecular changes that contribute to senescence. Such understanding also helps to clarify how the genome shapes the ageing process, thereby aiding the study of the genetic facto...
journal_title：Nature
pub_type： 杂志文章,评审
doi：10.1038/35041682
更新日期：2000-11-09 00:00:00
abstract：:Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/355735a0
更新日期：1992-02-20 00:00:00
abstract：:In the ocean, the chemical forms of nitrogen that are readily available for biological use (known collectively as 'fixed' nitrogen) fuel the global phytoplankton productivity that exports carbon to the deep ocean. Accordingly, variation in the oceanic fixed nitrogen reservoir has been proposed as a cause of glacial-in...
journal_title：Nature
pub_type： 历史文章,杂志文章
doi：10.1038/nature12397
更新日期：2013-09-12 00:00:00
abstract：:The extinction rate of populations is predicted to rise under increasing rates of environmental change. If a population experiencing increasingly stressful conditions lacks appropriate phenotypic plasticity or access to more suitable habitats, then genetic change may be the only way to avoid extinction. Evolutionary r...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature11879
更新日期：2013-02-28 00:00:00
abstract：:Somatic cell nuclear transfer (SCNT) into enucleated oocytes has emerged as a technique that can be used to derive mouse embryonic stem cell lines with defined genotypes. In this issue Byrne et al. report the derivation of two SCNT Rhesus macaca male stem cell lines designated CRES-1 and CRES-2. Molecular studies deta...
journal_title：Nature
pub_type： 评论,杂志文章
doi：10.1038/nature06456
更新日期：2007-11-22 00:00:00
abstract：:Amino-acid radicals play key roles in many enzymatic reactions. Catalysis often involves transfer of a radical character within the protein, as in class I ribonucleotide reductase where radical transfer occurs over 35 A, from a tyrosyl radical to a cysteine. It is currently debated whether this kind of long-range tran...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35014644
更新日期：2000-06-01 00:00:00
abstract：:The variable (V) regions of heavy and light immunoglobulin chains are encoded by multiple germline DNA elements which are assembled into complete variable-region genes in precursor(pre-) B lymphocytes. The heavy-chain V region (VH) is assembled from three separate germline DNA elements, the variable (VH), diversity (D...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/317353a0
更新日期：1985-09-26 00:00:00
abstract：:Time-of-flight mass spectrometry-most notably matrix-assisted laser-desorption-ionization time-of-flight (MALDI-TOF) spectrometry-is an important class of techniques for the study of proteins and other biomolecules. Although these techniques provide excellent performance for masses up to about 20,000 daltons, there ha...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35582
更新日期：1998-02-12 00:00:00
abstract：:Ecdysone in Drosophila has been a paradigm for steroid hormones since its ability to induce gene activity directly was demonstrated by its effects on moulting and polytene chromosome puffing. The ecdysone receptor (EcR) was recently confirmed as a member of the nuclear receptor superfamily by cloning and characterizat...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/362471a0
更新日期：1993-04-01 00:00:00
abstract：:There is increasing evidence for the process of sympatric speciation, in which reproductive isolation of species occurs without physical isolation. Theoretical models have focused on disruptive natural selection as the crucial pressure for splitting a species. Here we report the theoretical finding that sympatric spec...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/990087
更新日期：1999-12-02 00:00:00
abstract：:The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed product...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02374
更新日期：2004-03-18 00:00:00
abstract：:The paired helical filament (PHF) is the major component of the neurofibrillary deposits that form a defining neuropathological characteristic of Alzheimer's disease. PHFs are composed of microtubule-associated protein tau, in a hyperphosphorylated state. Hyperphosphorylation of tau results in its inability to bind to...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/383550a0
更新日期：1996-10-10 00:00:00
abstract：:Nuclear import of the NF-AT transcription factors during T-cell activation requires the calcium-activated phosphatase calcineurin, which unmasks nuclear-location signals on NF-AT. We show here that the nuclear import of NF-ATs is not sufficient to activate NF-AT target genes, as NF-ATs are subject to a futile cycling ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/18473
更新日期：1999-03-18 00:00:00
abstract：:Hereditary nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases. Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease. In particular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were sh...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/371075a0
更新日期：1994-09-01 00:00:00
abstract：:Since at least the last common ancestor of all life on Earth, genetic information has been stored in a four-letter alphabet that is propagated and retrieved by the formation of two base pairs. The central goal of synthetic biology is to create new life forms and functions, and the most general route to this goal is th...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature24659
更新日期：2017-11-29 00:00:00
abstract：:An ongoing challenge in chemical research is to design catalysts that select the outcomes of the reactions of complex molecules. Chemists rely on organocatalysts or transition metal catalysts to control stereoselectivity, regioselectivity and periselectivity (selectivity among possible pericyclic reactions). Nature ac...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2743-5
更新日期：2020-10-01 00:00:00
abstract：:The horizontal separation of the eyes means that objects nearer or farther than the fixation point project to different locations on the two retinae, differing principally in their horizontal coordinates (horizontal binocular disparity). Disparity-selective neurons have generally been studied with disparities applied ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature00909
更新日期：2002-08-08 00:00:00
abstract：:An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature11133
更新日期：2012-05-23 00:00:00
abstract：:Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxy-peptidase that generates the vasoconstricting peptide angiotensin II and inactivates the vasodilating peptide bradykinin. The gene encoding ACE is composed of two homologous regions and codes for both a somatic and testis isoenzyme. Experiments with hypertens...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/375146a0
更新日期：1995-05-11 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/d41586-019-00219-5
更新日期：2019-01-01 00:00:00
abstract：:Phosphorylation of myosin light chains by a calmodulin-myosin light-chain kinase (MLCK) pathway is considered to be responsible for coupling increased calcium concentration with contraction in smooth muscle. This simple view has, however, recently been questioned. To test this hypothesis directly, we microinjected ind...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/338164a0
更新日期：1989-03-09 00:00:00
