Abstract：
:Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.
journal_name
Naturejournal_title
Natureauthors
Schatton T,Murphy GF,Frank NY,Yamaura K,Waaga-Gasser AM,Gasser M,Zhan Q,Jordan S,Duncan LM,Weishaupt C,Fuhlbrigge RC,Kupper TS,Sayegh MH,Frank MHdoi
10.1038/nature06489subject
Has Abstractpub_date
2008-01-17 00:00:00pages
345-9issue
7176eissn
0028-0836issn
1476-4687pii
nature06489journal_volume
451pub_type
杂志文章相关文献
NATURE文献大全abstract：:The origin of cooperation is a central challenge to our understanding of evolution. The fact that microbial interactions can be manipulated in ways that animal interactions cannot has led to a growing interest in microbial models of cooperation and competition. For the budding yeast Saccharomyces cerevisiae to grow on...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07921
更新日期：2009-05-14 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-07706-1
更新日期：2018-12-01 00:00:00
abstract：:Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07179
更新日期：2008-09-25 00:00:00
abstract：:An increase in free calcium triggers catecholamine secretion from chromaffin cells and calmodulin is strongly implicated as the intracellular Ca2+ receptor. In our recent studies of calmodulin action in the chromaffin cell, micromolar Ca2+ concentrations resulted in calmodulin and cytosolic proteins becoming bound to ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/301432a0
更新日期：1983-02-03 00:00:00
abstract：:Expansion of anthropogenic noise and night lighting across our planet1,2 is of increasing conservation concern3-6. Despite growing knowledge of physiological and behavioural responses to these stimuli from single-species and local-scale studies, whether these pollutants affect fitness is less clear, as is how and why ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2903-7
更新日期：2020-11-01 00:00:00
abstract：:Many natural habitats exist on privately owned land outside protected areas, but few governments can afford to enforce or subsidize conservation of this biodiversity. Even in some developed countries, conservation subsidy schemes have only achieved limited success. Fortunately, some landowners may be willing to accept...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01678
更新日期：2003-05-29 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-07463-1
更新日期：2018-11-01 00:00:00
abstract：:Post-translational modification (PTM) of proteins plays an important part in mediating protein interactions and/or the recruitment of specific protein targets. PTM can be mediated by the addition of functional groups (for example, acetylation or phosphorylation), peptides (for example, ubiquitylation or sumoylation), ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature06420
更新日期：2008-01-03 00:00:00
abstract：:The microscopic origin of superconductivity in the high-transition-temperature (high-T(c)) copper oxides remains the subject of active inquiry; several of their electronic characteristics are well established as universal to all the known materials, forming the experimental foundation that all theories must address. T...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01877
更新日期：2003-07-31 00:00:00
abstract：:The direct involvement of the pituitary-adrenal axis in birth has been well established, at least in sheep, and its removal prolongs pregnancy. As part of the process the fetal sheep adrenal grows rapidly during the 10-15 d prepartum and is associated with a large rise in the plasma corticosteroid concentration. This ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/284616a0
更新日期：1980-04-17 00:00:00
abstract：:Retinoid X receptor (RXR) plays a central role in the regulation of many intracellular receptor signalling pathways and can mediate ligand-dependent transcription, acting as a homodimer or as a heterodimer. Here we identify an antagonist towards RXR homodimers which also functions as an agonist when RXR is paired as a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/383450a0
更新日期：1996-10-03 00:00:00
abstract：:Self-reproduction is central to biological life for long-term sustainability and evolutionary adaptation. Although these traits would also be desirable in many engineered systems, the principles of self-reproduction have not been exploited in machine design. Here we create simple machines that act as autonomous modula...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/435163a
更新日期：2005-05-12 00:00:00
abstract：:Phenylketonuria (PKU) is an autosomal recessive human genetic disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase, EC 1.14.16.1). PKU is a common inborn error of amino-acid metabolism in caucasian populations and approximately 1 in 50 individuals are carriers of a P...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/327333a0
更新日期：1987-05-28 00:00:00
abstract：:The kinesin superfamily is a class of microtubule-based mechano-enzymes involved in intracellular transport and chromosome movements. Molecules that move towards either the plus end or the minus end of microtubules are represented within the family. The motor domains of these molecules exhibit considerable sequence ho...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/376271a0
更新日期：1995-07-20 00:00:00
abstract：:Cyclic ADP-ribose (cADPR) is a newly identified nucleotide which can release calcium from a variety of cells, suggesting it is a messenger for mobilizing internal Ca2+ stores. Its cyclic structure has now been confirmed by X-ray crystallography. Available results are consistent with it being a modulator of Ca(2+)-indu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/370307a0
更新日期：1994-07-28 00:00:00
abstract：:Since the discovery of superconductivity in the high-transition-temperature (high-T(c)) copper oxides two decades ago, it has been firmly established that the CuO(2) plane is essential for superconductivity and gives rise to a host of other very unusual properties. A new family of superconductors with the general comp...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07081
更新日期：2008-06-26 00:00:00
abstract：:Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is tr...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature08028
更新日期：2009-06-11 00:00:00
abstract：:According to the generally accepted scenario, the last giant impact on Earth formed the Moon and initiated the final phase of core formation by melting Earth's mantle. A key goal of geochemistry is to date this event, but different ages have been proposed. Some argue for an early Moon-forming event, approximately 30 m...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13172
更新日期：2014-04-03 00:00:00
abstract：:Circumstellar accretion disks transfer matter from molecular clouds to young stars and to the sites of planet formation. The disks observed around pre-main-sequence stars have properties consistent with those expected for the pre-solar nebula from which our own Solar System formed 4.5 Gyr ago. But the 'debris' disks t...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35051033
更新日期：2001-01-04 00:00:00
abstract：:Common genetic contributions to autism spectrum disorder (ASD) reside in risk gene variants that individually have minimal effect sizes. As environmental factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial to identify altered regulators that can orchestrate multiple ASD risk genes during ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-018-0423-5
更新日期：2018-08-01 00:00:00
abstract：:Magnetic fields play a part in almost all stages of stellar evolution. Most low-mass stars, including the Sun, show surface fields that are generated by dynamo processes in their convective envelopes. Intermediate-mass stars do not have deep convective envelopes, although 10 per cent exhibit strong surface fields that...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature16171
更新日期：2016-01-21 00:00:00
abstract：:Multiple sclerosis is commonly associated with a local humoral immune response within the central nervous system. A hallmark of this intrathecal response is the presence of electrophoretically demonstrable oligoclonal bands of IgG in the cerebrospinal fluid (CSF) of up to 95% of patients. Observations indicating that ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/338769a0
更新日期：1989-04-27 00:00:00
abstract：:Glycine is an important inhibitory transmitter in the brainstem and spinal cord. In the trigeminal subnucleus caudalis (medullary dorsal horn) and in the spinal dorsal horn (the relaying centres for processing pain and sensory information), glycine inhibits the glutamate-evoked depolarization and depresses firing of n...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/348242a0
更新日期：1990-11-15 00:00:00
abstract：:An Amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41586-019-1890-z
更新日期：2020-01-01 00:00:00
abstract：:Many proteins are expressed in distinct embryonic and adult forms. However, in most cases we do not know why the embryonic form of proteins is required. This question can be readily addressed for the acetylcholine receptor (AChR) because developmentally specified modifications of this ligand-gated ion channel can be d...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/335066a0
更新日期：1988-09-01 00:00:00
abstract：:Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, an...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature25015
更新日期：2018-01-04 00:00:00
abstract：:Metallothioneins are small cysteine-rich proteins that bind heavy metals such as zinc, cadmium, copper and mercury. Recent interest in these proteins has focused on the part they play in zinc metabolism and heavy metal detoxification. Our interest in metallothionein genes stems largely from the observations that these...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/292267a0
更新日期：1981-07-16 00:00:00
abstract：:Modification of tyrosine residues of proteins has attracted great interest. Although phosphorylation has received most attention, tyrosine-O-sulphation is also common and has been closely investigated in the hormones gastrin and cholecystokinin (CCK). CCK regulates pancreatic enzyme secretion. It is always sulphated a...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/309456a0
更新日期：1984-05-31 00:00:00
abstract：:The origins of religion and of complex societies represent evolutionary puzzles1-8. The 'moralizing gods' hypothesis offers a solution to both puzzles by proposing that belief in morally concerned supernatural agents culturally evolved to facilitate cooperation among strangers in large-scale societies9-13. Although pr...
journal_title：Nature
pub_type： 历史文章,杂志文章
doi：10.1038/s41586-019-1043-4
更新日期：2019-04-01 00:00:00
abstract：:The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders1-4. Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-2192-1
更新日期：2020-05-01 00:00:00
