Abstract:
:Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch2 is highly expressed in glioblastoma multiforme (GBM), a highly malignant astrocytoma. It is therefore conceivable that increased Notch2 signaling in NSCs contributes to the formation of GBM. Here, we demonstrate that mice constitutively expressing the activated intracellular domain of Notch2 in NSCs display a hyperplasia of the neurogenic niche and reduced neuronal lineage entry. Neurospheres derived from these mice show increased proliferation, survival and resistance to apoptosis. Moreover, they preferentially differentiate into astrocytes, which are the characteristic cellular population of astrocytoma. Likewise, we show that Notch2 signaling increases proliferation and resistance to apoptosis in human GBM cell lines. Gene expression profiling of GBM patient tumor samples reveals a positive correlation of Notch2 transcripts with gene transcripts controlling anti-apoptotic processes, stemness and astrocyte fate, and a negative correlation with gene transcripts controlling proapoptotic processes and oligodendrocyte fate. Our data show that Notch2 signaling in NSCs produces features of GSCs and induces astrocytic lineage entry, consistent with a possible role in astrocytoma formation.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Tchorz JS,Tome M,Cloëtta D,Sivasankaran B,Grzmil M,Huber RM,Rutz-Schatzmann F,Kirchhoff F,Schaeren-Wiemers N,Gassmann M,Hemmings BA,Merlo A,Bettler Bdoi
10.1038/cddis.2012.65subject
Has Abstractpub_date
2012-06-21 00:00:00pages
e325issn
2041-4889pii
cddis201265journal_volume
3pub_type
杂志文章abstract::Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0373-8
更新日期:2018-02-20 00:00:00
abstract::Traumatic brain injury (TBI) activates multiple neuronal cell death mechanisms, leading to post-traumatic neuronal loss and neurological deficits. TBI-induced cell cycle activation (CCA) in post-mitotic neurons causes regulated cell death involving cyclin-dependent kinase (CDK) activation and initiation of an E2F tran...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1156-y
更新日期:2018-11-06 00:00:00
abstract::P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), has been found to regulate numerous cell signaling pathways controlling cell fate by acetylating both histone and non-histone proteins. We previously reported that PCAF upregulates cell apoptosis by inactivating Serine/Threonine Protein Kinase 1 (AK...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.76
更新日期:2015-04-09 00:00:00
abstract::The majority of developmentally programmed cell death (PCD) is mediated by caspase-dependent apoptosis; however, additional modalities, including autophagy-dependent cell death, have important spatiotemporally restricted functions. Autophagy involves the engulfment of cytoplasmic components in a double membrane vesicl...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1368-9
更新日期:2019-02-08 00:00:00
abstract::The most common complication after cataract surgery is postoperative capsular opacification, which includes anterior capsular opacification (ACO) and posterior capsular opacification (PCO). Increased adhesion of lens epithelial cells (LECs) to the intraocular lens material surface promotes ACO formation, whereas proli...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.315
更新日期:2017-07-13 00:00:00
abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.495
更新日期:2013-12-19 00:00:00
abstract::The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inh...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.233
更新日期:2017-06-15 00:00:00
abstract::Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.228
更新日期:2014-05-29 00:00:00
abstract::Tumor-associated macrophages (TAMs) are frequently found near pancreatic cancer cells, but it is uncertain whether they are involved in pancreatic cancer progression and the Warburg effect. Here, we show that CCL18 secreted by TAMs facilitates malignant progression and induced a glycolytic phenotype in pancreatic canc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0486-0
更新日期:2018-05-01 00:00:00
abstract::The biological clock is an endogenous biological timing system, which controls metabolic functions in almost all organs. Nutrient metabolism, substrate processing, and detoxification are circadian controlled in livers. However, how the clock genes respond to toxins and influence toxicity keeps unclear. We identified t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03343-7
更新日期:2021-01-12 00:00:00
abstract::The Pierre Robin Sequence (PRS), consisting of cleft palate, glossoptosis and micrognathia, is a common human birth defect. However, how this abnormality occurs remains largely unknown. Here we report that neural crest cell (NCC)-specific knockout of transferrin receptor (Tfrc), a well known transferrin transporter pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.170
更新日期:2016-06-30 00:00:00
abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0534-9
更新日期:2018-05-01 00:00:00
abstract::Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.155
更新日期:2017-04-06 00:00:00
abstract::Cytotoxic T lymphocytes (CTL) and natural killer cells (NK)-mediated elimination of tumor cells is mostly dependent on Granzyme B apoptotic pathway, which is regulated by the wild type (wt) p53 protein. Because TP53 inactivating mutations, frequently found in human tumors, could interfere with Granzyme B-mediated cell...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1950-1
更新日期:2019-09-20 00:00:00
abstract::The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. Although this proposition is supported by the clinical success of proteasome inhibitors in some malignancies, most cancers are resistant to proteasome inhibition. The ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.373
更新日期:2015-12-31 00:00:00
abstract::The role of autophagy in cancer onset and progression appears still controversial. On one hand, autophagy allows cancer cell to survive in unfavorable environmental conditions, on the other hand, once internal energy resources are exhausted, it leads to cell death. In addition, autophagy interpheres with cell cycle pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0864-7
更新日期:2018-08-06 00:00:00
abstract::miR-195 has recently been reported to function as a tumor suppressor in various cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms by which miR-195 represses the tumorigenesis of NSCLC cells are not fully understood. We performed a high-throughput screen using an miRNA mimic library and con...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0219-9
更新日期:2018-02-07 00:00:00
abstract::The original version of this Article contained an error in Fig. 1, in which a number of incorrect fluorescence images were inadvertently incorporated into the panel. This has been corrected in both the PDF and HTML versions of the Article. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1422-7
更新日期:2019-03-12 00:00:00
abstract::Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2644-4
更新日期:2020-06-08 00:00:00
abstract::MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and prol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.370
更新日期:2014-09-11 00:00:00
abstract::Betulinic acid (BA) exhibits cytotoxic activity against some cancer cells. However, the molecular mechanism of BA against CRC cells was little reported. Here, we proved that BA elicited CRC cells' growth inhibition and apoptosis in a dose-dependent manner. In addition, BA treatment induced autophagy via inhibiting the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.485
更新日期:2017-10-05 00:00:00
abstract::Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2009.18
更新日期:2010-01-01 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::The nuclear localization signal (NLS) in kinesin-14 KIFC1 is associated with nuclear importins and Ran gradient, but detailed mechanism remains unknown. In this study, we found that KIFC1 proteins have specific transport characteristics during cell cycle. In the absence of KIFC1, cell cycle kinetics decrease significa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1619-9
更新日期:2019-05-24 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in hum...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.66
更新日期:2014-03-20 00:00:00
abstract::Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-assoc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02915-x
更新日期:2020-08-26 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, bu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.417
更新日期:2014-10-09 00:00:00
abstract::Metabolic syndrome (MetS) is a complex, emerging epidemic which disrupts the metabolic homeostasis of several organs, including liver, heart, pancreas, and adipose tissue. While studies have been conducted in these research areas, the pathogenesis and mechanisms of MetS remain debatable. Lines of evidence show that ph...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2275-9
更新日期:2020-02-03 00:00:00
abstract::CCAAT/enhancer binding protein beta (C/EBPβ), a transcription factor expressed in muscle satellite cells (SCs), inhibits the myogenic program and is downregulated early in differentiation. In a conditional null model in which C/EBPβ expression is knocked down in paired box protein 7+ (Pax7+) SCs, cardiotoxin (CTX) inj...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.4
更新日期:2016-02-25 00:00:00
abstract::It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of decreased auto...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0445-9
更新日期:2018-03-14 00:00:00