Abstract:
:Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs. Aside from the previously identified miR-200 family, these include the miR-15/16 (miR-16, miR-15b) and miR-103/107 (miR-103, miR-107) families as well as miR-145, miR-335, and miR-128b. Interestingly, these miRNAs affect common target genes that encode the Bmi1 and Suz12 components of the polycomb repressor complexes as well as the DNA-binding transcription factors Zeb1, Zeb2, and Klf4. Conversely, expression of the CSC-modulating miRNAs is inhibited by Zeb1 and Zeb2. There is an inverse relationship between the levels of CSC-regulating miRNAs and their respective targets in samples from triple-negative breast cancer patients, providing evidence for the relevance of these interactions in human cancer. In addition, combinatorial overexpression of these miRNAs progressively attenuates the growth of CSCs derived from triple-negative breast cancers. These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Polytarchou C,Iliopoulos D,Struhl Kdoi
10.1073/pnas.1212811109subject
Has Abstractpub_date
2012-09-04 00:00:00pages
14470-5issue
36eissn
0027-8424issn
1091-6490pii
1212811109journal_volume
109pub_type
杂志文章abstract::Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in ast...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.13.5178
更新日期:1989-07-01 00:00:00
abstract::Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1621400114
更新日期:2017-02-14 00:00:00
abstract::Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究
doi:10.1073/pnas.1118051109
更新日期:2012-04-17 00:00:00
abstract::This presentation reviews Chandra's major contribution to the understanding of nearby galaxies. After a brief summary on significant advances in characterizing various types of discrete x-ray sources, the presentation focuses on the global hot gas in and around galaxies, especially normal ones like our own. The hot ga...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0914255107
更新日期:2010-04-20 00:00:00
abstract::Nuclease resistance and RNA affinity are key criteria in the search for optimal antisense nucleic acid modifications, but the origins of the various levels of resistance to nuclease degradation conferred by chemical modification of DNA and RNA are currently not understood. The 2'-O-aminopropyl (AP)-RNA modification di...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.25.14240
更新日期:1999-12-07 00:00:00
abstract::Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dys...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1512968112
更新日期:2015-12-08 00:00:00
abstract::Our research addresses the relationship between subnuclear localization and gene expression in fission yeast. We observed the relocalization of a heterochromatic region, the mating-type region, from its natural location at the spindle-pole body to the immediate vicinity of the nucleolus. Relocalization occurred in res...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1315581110
更新日期:2013-11-19 00:00:00
abstract::Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1525677113
更新日期:2016-02-23 00:00:00
abstract::Aire induces ectopic expression of peripheral tissue antigens (PTAs) in thymic medullary epithelial cells, which promotes immunological tolerance. Beginning with a broad screen of histone peptides, we demonstrate that the mechanism by which this single factor controls the transcription of thousands of genes involves r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0808470105
更新日期:2008-10-14 00:00:00
abstract::Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulator...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1710877114
更新日期:2017-12-05 00:00:00
abstract::Injection of antisense oligonucleotides was used to investigate the function of c-mos in murine oocytes. Oocytes injected with antisense c-mos oligonucleotides completed the first meiotic division but failed to initiate meiosis II. Instead, loss of c-mos function led to chromosome decondensation, reformation of a nucl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.18.7038
更新日期:1989-09-01 00:00:00
abstract::Distributions of sulfur isotopes in geological samples would provide a record of atmospheric composition if the mechanism producing the isotope effects could be described quantitatively. We determined the UV absorption spectra of 32SO2, 33SO2, and 34SO2 and use them to interpret the geological record. The calculated i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0903518106
更新日期:2009-09-01 00:00:00
abstract::The oxygen isotope record of the last million years, as provided by a deep sea core sediment, is analyzed by a method recently developed in the theory of dynamical systems. The analysis suggests that climatic variability is the manifestation of a chaotic dynamics described by an attractor of fractal dimensionality. A ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.3.536
更新日期:1986-02-01 00:00:00
abstract::The dendritic building blocks with a focal pyrene unit self-organize into vesicles in aqueous phase. The in situ inclusion of the focal pyrene units into the cavity of beta- or gamma-cyclodextrin (CD) induces self-assembled organic nanotubes with an average outer diameter of approximately 45 nm and inner diameter of 2...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0505364103
更新日期:2006-01-31 00:00:00
abstract::Although most experimental and theoretical studies of protein folding involve proteins in vitro, the effects of spatial confinement may complicate protein folding in vivo. In this study, we examine the folding dynamics of villin (a small fast folding protein) with explicit solvent confined to an inert nanopore. We hav...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0608256104
更新日期:2007-06-19 00:00:00
abstract::The molecular mechanism of tolerance to opiate drugs is poorly understood. We have used single-channel patch-clamp recordings to study opiate receptor effects on dissociated neurons from rat amygdala, a limbic region implicated in addiction processes. A 130-pS inwardly rectifying K(+)-preferring cation channel was act...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.26.14692
更新日期:2000-12-19 00:00:00
abstract::Cell-specific activation of the transcription factor sigma F during sporulation in Bacillus subtilis is controlled by a regulatory pathway involving the proteins SpoIIE, SpoIIAA, and SpoIIAB. SpoIIAB is an antagonist of sigma F, and SpoIIAA, which is capable of overcoming SpoIIAB-mediated inhibition of sigma F, is an ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.8.3238
更新日期:1996-04-16 00:00:00
abstract::A MODEL OF THE LINEAR HYDROGEN BOND HAS BEEN DEVISED WHICH IS CHARACTERIZED BY THREE PHYSICAL PARAMETERS OF THE ISOLATED ELECTRON DONOR AND PROTON DONOR MOLECULES: mu(A-H), the bond dipole moment; DeltaI, the difference in ionization potential between that of the electron donor and the corresponding noble gas atom; an...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.12.4701
更新日期:1975-12-01 00:00:00
abstract::The formation of complex but highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1706533114
更新日期:2017-07-18 00:00:00
abstract::During the last 15 years several laboratories have attempted to generate rabbit monoclonal antibodies, mainly because rabbits recognize antigens and epitopes that are not immunogenic in mice or rats, two species from which monoclonal antibodies are usually generated. Monoclonal antibodies from rabbits could not be gen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.20.9348
更新日期:1995-09-26 00:00:00
abstract::It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to ge...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1720658115
更新日期:2018-05-01 00:00:00
abstract::A fundamental mystery of plant cell biology is the occurrence of "stromules," stroma-filled tubular extensions from plastids (such as chloroplasts) that are universally observed in plants but whose functions are, in effect, completely unknown. One prevalent hypothesis is that stromules exchange signals or metabolites ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1511570112
更新日期:2015-08-11 00:00:00
abstract::Micron-scale robots require systems that can morph into arbitrary target configurations controlled by external agents such as heat, light, electricity, and chemical environment. Achieving this behavior using conventional approaches is challenging because the available materials at these scales are not programmable lik...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1922635117
更新日期:2020-04-21 00:00:00
abstract::Down-regulation of mitogenic signaling in mammalian cells relies in part on endosomal trafficking of activated receptors into lysosomes, where the receptors are degraded. These events are mediated by ubiquitination of the endosomal cargo and its consequent sorting into multivesicular bodies that form at the surfaces o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0932599100
更新日期:2003-06-24 00:00:00
abstract::In some countries across the globe, tropical forest cover is increasing. The national-scale reforestation of Vietnam since 1992 is assumed to contribute to this recovery. It is achieved, however, by the displacement of forest extraction to other countries on the order of 49 (34-70) M m(3), or approximately 39% of the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904942106
更新日期:2009-09-22 00:00:00
abstract::Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calci...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0801027105
更新日期:2008-04-01 00:00:00
abstract::Mutations are introduced into rearranged Ig variable genes at a frequency of 10(-2) mutations per base pair by an unknown mechanism. Assuming that DNA repair pathways generate or remove mutations, the frequency and pattern of mutation will be different in variable genes from mice defective in repair. Therefore, hyperm...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.12.6953
更新日期:1998-06-09 00:00:00
abstract::The inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum mediates calcium signaling that impinges on intracellular processes. IP3Rs are allosteric proteins comprising four subunits that form an ion channel activated by binding of IP3 at a distance. Defective allostery in IP3R is considered crucial...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1409730111
更新日期:2014-09-23 00:00:00
abstract::A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0907511106
更新日期:2009-11-24 00:00:00
abstract::Eusociality is a major evolutionary innovation involving alterations in life history, morphology, and behavior. Advanced eusocial insects, such as ants, termites, and corbiculate bees, cannot provide insights into the earliest stages of eusocial evolution because eusociality in these taxa evolved long ago (in the Cret...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.012387999
更新日期:2002-01-08 00:00:00