Abstract:
:In glioblastoma, invasion and proliferation are presumed to be mutually exclusive events; however, the molecular mechanisms that mediate this switch at the cellular level remain elusive. Previously, we have shown that phospho-OLIG2, a central-nervous-system-specific transcription factor, is essential for tumor growth and proliferation. Here, we show that the modulation of OLIG2 phosphorylation can trigger a switch between proliferation and invasion. Glioma cells with unphosphorylated OLIG2(S10, S13, S14) are highly migratory and invasive, both in vitro and in vivo. Mechanistically, unphosphorylated OLIG2 induces TGF-β2 expression and promotes invasive mesenchymal properties in glioma cells. Inhibition of the TGF-β2 pathway blocks this OLIG2-dependent invasion. Furthermore, ectopic expression of phosphomimetic Olig2 is sufficient to block TGF-β2-mediated invasion and reduce expression of invasion genes (ZEB1 and CD44). Our results not only provide a mechanistic insight into how cells switch from proliferation to invasion but also offer therapeutic opportunities for inhibiting dissemination of gliomas.
journal_name
Cell Repjournal_title
Cell reportsauthors
Singh SK,Fiorelli R,Kupp R,Rajan S,Szeto E,Lo Cascio C,Maire CL,Sun Y,Alberta JA,Eschbacher JM,Ligon KL,Berens ME,Sanai N,Mehta Sdoi
10.1016/j.celrep.2016.06.045subject
Has Abstractpub_date
2016-07-26 00:00:00pages
950-966issue
4issn
2211-1247pii
S2211-1247(16)30799-9journal_volume
16pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Building an integrated view of cellular responses to environmental cues remains a fundamental challenge due to the complexity of intracellular networks in mammalian cells. Here, we introduce an integrative biochemical and genetic framework to dissect signal transduction events using multiple data types and, in particu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.06.016
更新日期:2017-06-27 00:00:00
abstract::Specific cellular fates and functions depend on differential gene expression, which occurs primarily at the transcriptional level and is controlled by complex regulatory networks of transcription factors (TFs). TFs act through combinatorial interactions with other TFs, cofactors, and chromatin-remodeling proteins. Her...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.08.038
更新日期:2014-09-25 00:00:00
abstract::Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects rem...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.09.030
更新日期:2016-10-11 00:00:00
abstract::Chromatin interactions play important roles in transcription regulation. To better understand the underlying evolutionary and functional constraints of these interactions, we implemented a systems approach to examine RNA polymerase-II-associated chromatin interactions in human cells. We found that 40% of the total gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.09.022
更新日期:2012-11-29 00:00:00
abstract::Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish mic...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.06.018
更新日期:2013-07-25 00:00:00
abstract::Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 m...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.065
更新日期:2018-03-13 00:00:00
abstract::Inhibitory receptors (IRs) function as critical regulators of immune responses by tempering T cell activity. In humans, several persisting viruses as well as cancers exploit IR signaling by upregulating IR ligands, resulting in suppression of T cell function (i.e., exhaustion). This allows escape from immune surveilla...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.10.119
更新日期:2019-12-03 00:00:00
abstract::Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multisite phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phospho...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.12.003
更新日期:2014-01-16 00:00:00
abstract::Ubiquitin and ubiquitin-like chains are finely balanced by conjugating and de-conjugating enzymes. Alterations in this balance trigger the response to stress conditions and are often observed in pathologies. How such changes are detected is not well understood. We identify the HSP70 chaperone as a sensor of changes in...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.08.070
更新日期:2019-10-01 00:00:00
abstract::The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6), promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.08.006
更新日期:2016-09-06 00:00:00
abstract::Brain function is compromised in myotonic dystrophy type 1 (DM1), but the underlying mechanisms are not fully understood. To gain insight into the cellular and molecular pathways primarily affected, we studied a mouse model of DM1 and brains of adult patients. We found pronounced RNA toxicity in the Bergmann glia of t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.06.006
更新日期:2017-06-27 00:00:00
abstract::The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.10.074
更新日期:2017-11-14 00:00:00
abstract::Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here, we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol leve...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.10.033
更新日期:2015-11-24 00:00:00
abstract::Bacterial genes that change in expression upon environmental disturbance have commonly been seen as those that must also phenotypically matter. However, several studies suggest that differentially expressed genes are rarely phenotypically important. We demonstrate, for Gram-positive and Gram-negative bacteria, that th...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.07.062
更新日期:2017-08-15 00:00:00
abstract::In many organs, stem cell function depends on communication with their niche partners. Cranial sensory neurons develop in close proximity to blood vessels; however, whether vasculature is an integral component of their niches is yet unknown. Here, two separate roles for vasculature in cranial sensory neurogenesis in z...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107903
更新日期:2020-07-14 00:00:00
abstract::Poverty, displacement, and parental stress represent potent sources of early life stress (ELS). Stress disproportionately affects females, who are at increased risk for stress-related pathologies associated with cognitive impairment. Mechanisms underlying stress-associated cognitive impairment and enhanced risk of fem...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.010
更新日期:2018-11-27 00:00:00
abstract::Lung disease is a major cause of death in the United States, with current therapeutic approaches serving only to manage symptoms. The most common chronic and life-threatening genetic disease of the lung is cystic fibrosis (CF) caused by mutations in the cystic fibrosis transmembrane regulator (CFTR). We have generated...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.07.062
更新日期:2015-09-01 00:00:00
abstract::In neurons, transmembrane proteins are targeted to dendrites in vesicles that traffic solely within the somatodendritic compartment. How these vesicles are retained within the somatodendritic domain is unknown. Here, we use a novel pulse-chase system, which allows synchronous release of exogenous transmembrane protein...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.05.018
更新日期:2012-07-26 00:00:00
abstract::Either caspase-1 or caspase-11 can cleave gasdermin D to cause pyroptosis, eliminating intracellular replication niches. We previously showed that macrophages detect Burkholderia thailandensis via NLRC4, triggering the release of interleukin (IL)-18 and driving an essential interferon (IFN)-γ response that primes casp...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107967
更新日期:2020-07-28 00:00:00
abstract::Glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat type 2 diabetes mellitus often produce nausea, vomiting, and in some patients, undesired anorexia. Notably, these behavioral effects are caused by direct central GLP-1R activation. Herein, we describe the creation of a GLP-1R agonist conjugate with modif...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107768
更新日期:2020-06-16 00:00:00
abstract::Fc receptor for IgM (FcμR)-deficient mice display dysregulated function of neutrophils, dendritic cells, and B cells. The relevance of FcμR to human T cells is still unknown. We show that FcμR is mostly stored inside the cell and that surface expression is tightly regulated. Decreased surface expression on T cells fro...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.02.024
更新日期:2019-03-05 00:00:00
abstract::Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiqu...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.05.078
更新日期:2017-06-20 00:00:00
abstract::Maintaining genome integrity requires the accurate and complete replication of chromosomal DNA. This is of the utmost importance for embryonic stem cells (ESCs), which differentiate into cells of all lineages, including germ cells. However, endogenous and exogenous factors frequently induce stalling of replication for...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.01.014
更新日期:2014-02-27 00:00:00
abstract::Complex interactions between immune cells are an important component in the induction of obesity. Here, we show that Il2rg-/-Rag2-/- mice lacking all lymphocytes are resistant to diet-induced obesity. Transplantation of bone marrow cells from Rag2-/- mice, which lack only acquired immune cells, into Il2rg-/-Rag2-/- mi...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.06.016
更新日期:2019-07-02 00:00:00
abstract::Eukaryotic DNA replication licensing is a prerequisite for, and plays a role in, regulating genome duplication that occurs exactly once per cell cycle. ORC (origin recognition complex) binds to and marks replication origins throughout the cell cycle and loads other replication-initiation proteins onto replication orig...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.02.046
更新日期:2020-03-10 00:00:00
abstract::Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated a...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.08.028
更新日期:2016-09-13 00:00:00
abstract::Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulat...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.08.039
更新日期:2015-09-29 00:00:00
abstract::Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the ce...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.094
更新日期:2018-01-23 00:00:00
abstract::Mutations of WD40-repeat protein 62 (WDR62) have been identified recently to cause human MCPH (autosomal-recessive primary microcephaly), a neurodevelopmental disorder characterized by decreased brain size. However, the underlying mechanism is unclear. Here, we investigate the function of WDR62 in brain development an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2013.12.016
更新日期:2014-01-16 00:00:00
abstract::Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.06.005
更新日期:2014-07-10 00:00:00