Abstract：
:The tumour vascular microenvironment supports tumorigenesis not only by supplying oxygen and diffusible nutrients but also by secreting soluble factors that promote tumorigenesis. Here we identify a feedforward mechanism in which endothelial cells (ECs), in response to tumour-derived mediators, release angiocrines driving aberrant vascularization and glioblastoma multiforme (GBM) progression through a hypoxia-independent induction of hypoxia-inducible factor (HIF)-1α. Phosphorylation of profilin-1 (Pfn-1) at Tyr 129 in ECs induces binding to the tumour suppressor protein von Hippel-Lindau (VHL), and prevents VHL-mediated degradation of prolyl-hydroxylated HIF-1α, culminating in HIF-1α accumulation even in normoxia. Elevated HIF-1α induces expression of multiple angiogenic factors, leading to vascular abnormality and tumour progression. In a genetic model of GBM, mice with an EC-specific defect in Pfn-1 phosphorylation exhibit reduced tumour angiogenesis, normalized vasculature and improved survival. Moreover, EC-specific Pfn-1 phosphorylation is associated with tumour aggressiveness in human glioma. These findings suggest that targeting Pfn-1 phosphorylation may offer a selective strategy for therapeutic intervention of malignant solid tumours.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Fan Y,Potdar AA,Gong Y,Eswarappa SM,Donnola S,Lathia JD,Hambardzumyan D,Rich JN,Fox PLdoi
10.1038/ncb2954subject
Has Abstractpub_date
2014-05-01 00:00:00pages
445-56issue
5eissn
1465-7392issn
1476-4679pii
ncb2954journal_volume
16pub_type
杂志文章abstract：:Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but how they arise is not clear1,2. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Isolated PGCs have a profound reduct...
journal_title：Nature cell biology
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doi：10.1038/s41556-017-0017-8
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abstract：: ...
journal_title：Nature cell biology
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abstract：:Chromosome loss or gain is associated with a large number of solid cancers, providing genomic plasticity and thus adaptability to cancer cells. Numerical centrosome abnormalities arising from centrosome over-duplication or failed cytokinesis are a recognized cause of aneuploidy. In higher eukaryotic cells, the centros...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1735
更新日期：2008-06-01 00:00:00
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journal_title：Nature cell biology
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doi：10.1038/ncb1104-1062
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1001-891
更新日期：2001-10-01 00:00:00
abstract：:The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particu...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb3367
更新日期：2016-05-27 00:00:00
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journal_title：Nature cell biology
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journal_title：Nature cell biology
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1793
更新日期：2008-11-01 00:00:00
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journal_title：Nature cell biology
pub_type： 评论,杂志文章
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更新日期：2015-07-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2020-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1787
更新日期：2008-11-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35055085
更新日期：2001-02-01 00:00:00
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journal_title：Nature cell biology
pub_type： 社论
doi：10.1038/ncb1109-1273a
更新日期：2009-11-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35036406
更新日期：2000-10-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1921
更新日期：2009-09-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1038/ncb3524
更新日期：2017-05-31 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb772
更新日期：2002-04-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncb2231
更新日期：2011-06-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2019-09-01 00:00:00
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journal_title：Nature cell biology
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更新日期：2008-12-01 00:00:00
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journal_title：Nature cell biology
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doi：10.1038/ncb1705
更新日期：2008-04-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2007-03-01 00:00:00
abstract：:The GTPase dynamin plays an essential part in endocytosis by catalysing the fission of nascent clathrin-coated vesicles from the plasma membrane. Using preformed phosphatidylinositol-4,5-bisphosphate-containing lipid nanotubes as a membrane template for dynamin self-assembly, we investigate the conformational changes ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/8997
更新日期：1999-05-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35070129
更新日期：2001-04-01 00:00:00
abstract：:Here we evaluate the idea that the Golgi is in dynamic equilibrium with the endoplasmic reticulum (ER). In cytoplasts that lack the Golgi apparatus, no regrowth of the Golgi is observed, nor is any transport from the ER to the cell surface detected. However, introduction of the smallest measurable amount of Golgi (equ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35041089
更新日期：2000-11-01 00:00:00
abstract：:Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb746
更新日期：2002-02-01 00:00:00
abstract：:NMDA (N-methyl-D-aspartate) receptors (NMDARs) are targeted to dendrites and anchored at the post-synaptic density (PSD) through interactions with PDZ proteins. However, little is known about how these receptors are sorted from the endoplasmic reticulum and Golgi apparatus to the synapse. Here, we find that synapse-as...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb990
更新日期：2003-06-01 00:00:00
