Abstract:
:The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.
journal_name
Elifejournal_title
eLifeauthors
Angiolini F,Belloni E,Giordano M,Campioni M,Forneris F,Paronetto MP,Lupia M,Brandas C,Pradella D,Di Matteo A,Giampietro C,Jodice G,Luise C,Bertalot G,Freddi S,Malinverno M,Irimia M,Moulton JD,Summerton J,Chiapparinodoi
10.7554/eLife.44305subject
Has Abstractpub_date
2019-03-04 00:00:00issn
2050-084Xpii
44305journal_volume
8pub_type
杂志文章相关文献
eLife文献大全abstract::Kinesin-1 and cytoplasmic dynein are microtubule (MT) motors that transport intracellular cargoes. It remains unclear how these motors move along MTs densely coated with obstacles of various sizes in the cytoplasm. Here, we tested the ability of single and multiple motors to bypass synthetic obstacles on MTs in vitro....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48629
更新日期:2019-09-09 00:00:00
abstract::Evolutionary changes in transcription networks are an important source of diversity across species, yet the quantitative consequences of network evolution have rarely been studied. Here we consider the transcriptional 'rewiring' of the three GAL genes that encode the enzymes needed for cells to convert galactose to gl...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18981
更新日期:2016-09-10 00:00:00
abstract::Hepatitis B virus (HBV) is an important but difficult to study human pathogen. Most basics of the hepadnaviral life-cycle were unraveled using duck HBV (DHBV) as a model although DHBV has a capsid protein (CP) comprising ~260 rather than ~180 amino acids. Here we present high-resolution structures of several DHBV caps...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57277
更新日期:2020-08-14 00:00:00
abstract::Proprioception, the sense of body position, movement, and associated forces, remains poorly understood, despite its critical role in movement. Most studies of area 2, a proprioceptive area of somatosensory cortex, have simply compared neurons' activities to the movement of the hand through space. Using motion tracking...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48198
更新日期:2020-01-23 00:00:00
abstract::The Sae2/CtIP protein is required for efficient processing of DNA double-strand breaks that initiate homologous recombination in eukaryotic cells. Sae2/CtIP is also important for survival of single-stranded Top1-induced lesions and CtIP is known to associate directly with transcription-associated complexes in mammalia...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.42733
更新日期:2018-12-07 00:00:00
abstract::Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.40339
更新日期:2019-05-02 00:00:00
abstract::Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P2 and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26138
更新日期:2017-08-15 00:00:00
abstract::Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneou...
journal_title:eLife
pub_type: 杂志文章,多中心研究
doi:10.7554/eLife.15085
更新日期:2017-01-09 00:00:00
abstract::Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exh...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04494
更新日期:2015-01-20 00:00:00
abstract::In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other resear...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.13615
更新日期:2016-03-03 00:00:00
abstract::Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cereb...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.48702
更新日期:2019-09-06 00:00:00
abstract::A strain of budding yeast that contains one large chromosome reveals how the telomere capping complex CST maintains linear but not circular chromosomes. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60150
更新日期:2020-08-05 00:00:00
abstract::Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twis...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08352
更新日期:2015-06-08 00:00:00
abstract::Goal-directed behavior involves distributed neuronal circuits in the mammalian brain, including diverse regions of neocortex. However, the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood. Here, we recorded membrane potential of excitatory layer 2/3 pyramidal n...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.15798
更新日期:2016-06-21 00:00:00
abstract::The new open-access journal eLife has launched, making its first content available in PubMed Central. In addition to publishing science of the highest quality, the journal aims to improve both the peer-review process and the presentation of new research results. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00270
更新日期:2012-10-15 00:00:00
abstract::Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degra...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02555
更新日期:2014-06-12 00:00:00
abstract::Baboons, members of the genus Papio, comprise six closely related species distributed throughout sub-Saharan Africa and southwest Arabia. The species exhibit more ecological flexibility and a wider range of social systems than many other primates. This article summarizes our current knowledge of the natural history of...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.50989
更新日期:2019-11-12 00:00:00
abstract::To move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. Here, we use in vivo calcium imaging, electrophysiology, and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia. We find that leg motor neurons exhi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56754
更新日期:2020-06-03 00:00:00
abstract::Responses of sensory neurons represent stimulus information, but are also influenced by internal state. For example, when monkeys direct their attention to a visual stimulus, the response gain of specific subsets of neurons in visual cortex changes. Here, we develop a functional model of population activity to investi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08998
更新日期:2015-11-02 00:00:00
abstract::hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Usin...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19273
更新日期:2017-01-03 00:00:00
abstract::The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37202
更新日期:2018-09-07 00:00:00
abstract::Generating recombinant monoclonal antibodies (R-mAbs) from mAb-producing hybridomas offers numerous advantages that increase the effectiveness, reproducibility, and transparent reporting of research. We report here the generation of a novel resource in the form of a library of recombinant R-mAbs validated for neurosci...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.43322
更新日期:2019-01-22 00:00:00
abstract::It is widely argued that personalized instruction based on individual differences in learning styles or genetic predispositions could improve learning outcomes. However, this proposition has resisted clear demonstration in human studies, where it is difficult to control experience and quantify outcomes. Here, we take ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47216
更新日期:2019-09-17 00:00:00
abstract::Recurrent somatic mutations of H3F3A in aggressive pediatric high-grade gliomas generate K27M or G34R/V mutant histone H3.3. H3.3-G34R/V mutants are common in tumors with mutations in p53 and ATRX, an H3.3-specific chromatin remodeler. To gain insight into the role of H3-G34R, we generated fission yeast that express o...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.27406
更新日期:2017-07-18 00:00:00
abstract::The incubation period for typhoid, polio, measles, leukemia and many other diseases follows a right-skewed, approximately lognormal distribution. Although this pattern was discovered more than sixty years ago, it remains an open question to explain its ubiquity. Here, we propose an explanation based on evolutionary dy...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30212
更新日期:2017-12-21 00:00:00
abstract::Synaptic positions underlie precise circuit connectivity. Synaptic positions can be established during embryogenesis and sustained during growth. The mechanisms that sustain synaptic specificity during allometric growth are largely unknown. We performed forward genetic screens in C. elegans for regulators of this proc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55890
更新日期:2020-04-07 00:00:00
abstract::The mesiotemporal lobe (MTL) is implicated in many cognitive processes, is compromised in numerous brain disorders, and exhibits a gradual cytoarchitectural transition from six-layered parahippocampal isocortex to three-layered hippocampal allocortex. Leveraging an ultra-high-resolution histological reconstruction of ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.60673
更新日期:2020-11-04 00:00:00
abstract::The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57335
更新日期:2020-09-18 00:00:00
abstract::SUMO-modification of nuclear proteins has profound effects on gene expression. However, non-toxic chemical tools that modulate sumoylation in cells are lacking. Here, to identify small molecule sumoylation inhibitors we developed a cell-based screen that focused on the well-sumoylated substrate, human Liver Receptor H...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.09003
更新日期:2015-12-11 00:00:00
abstract::Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.02242
更新日期:2014-05-13 00:00:00