Abstract:
:Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and its association with tumor cell phenotypes remain largely unknown. Here we found that GSCs were more glycolytic than NSTCs, and voltage-dependent anion channel 2 (VDAC2), a mitochondrial membrane protein, was critical for metabolic switching between GSCs and NSTCs to affect their phenotypes. VDAC2 was highly expressed in NSTCs relative to GSCs and coupled a glycolytic rate-limiting enzyme platelet-type of phosphofructokinase (PFKP) on mitochondrion to inhibit PFKP-mediated glycolysis required for GSC maintenance. Disruption of VDAC2 induced dedifferentiation of NSTCs to acquire GSC features, including the enhanced self-renewal, preferential expression of GSC markers, and increased tumorigenicity. Inversely, enforced expression ofVDAC2 impaired the self-renewal and highly tumorigenic properties of GSCs. PFK inhibitor clotrimazole compromised the effect of VDAC2 disruption on glycolytic reprogramming and GSC phenotypic transition. Clinically, VDAC2 expression inversely correlated with glioma grades (Immunohistochemical staining scores of VDAC2 were 4.7 ± 2.8, 3.2 ± 1.9, and 1.9 ± 1.9 for grade II, grade III, and IV, respectively, p < 0.05 for all) and the patients with high expression of VDAC2 had longer overall survival than those with low expression of VDAC2 (p = 0.0008). In conclusion, we demonstrate that VDAC2 is a new glycolytic regulator controlling the phenotype transition between glioma stem cells and non-stem cells and may serves as a new prognostic indicator and a potential therapeutic target for glioma patients.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhou K,Yao YL,He ZC,Chen C,Zhang XN,Yang KD,Liu YQ,Liu Q,Fu WJ,Chen YP,Niu Q,Ma QH,Zhou R,Yao XH,Zhang X,Cui YH,Bian XW,Shi Y,Ping YFdoi
10.1038/s41419-018-1015-xsubject
Has Abstractpub_date
2018-09-24 00:00:00pages
988issue
10issn
2041-4889pii
10.1038/s41419-018-1015-xjournal_volume
9pub_type
杂志文章abstract::The voltage-gated K+ channel has key roles in the vasculature and in atrial excitability and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1....
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.568
更新日期:2017-11-02 00:00:00
abstract::Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found tha...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1312-z
更新日期:2019-01-28 00:00:00
abstract::Protein S-nitrosylation, the redox-based posttranslational modification of a cysteine thiol by the attachment of a nitric oxide (NO) group, is responsible for a variety of signaling effects. Dysregulation of S-nitrosylation may be directly linked to cancer apoptotic resistance and cancer therapy outcomes, emphasizing ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1561-x
更新日期:2019-04-15 00:00:00
abstract::Alternatively activated macrophages have been reported to be helpful to alleviate systematic lupus erythematosus (SLE), and azithromycin could serve as an immunomodulator by promoting alternatively activated macrophage phenotype. However, the effect of azithromycin in SLE and the involved mechanism remain undetermined...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1097-5
更新日期:2018-10-22 00:00:00
abstract::In response to infection, polymorphonuclear neutrophils (PMN) are recruited in the infectious sites, and employ three major strategies to fight against the microbes including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). NETs are a meshwork of chromatin fibers mixed with granule-derived antim...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0538-5
更新日期:2018-05-22 00:00:00
abstract::Drug resistance is a major problem in cancer therapy. A growing body of evidence demonstrates that the tumor microenvironment, including cancer-associated fibroblasts (CAFs), can modulate drug sensitivity in tumor cells. We examined the effect of primary human CAFs on p53 induction and cell viability in prostate cance...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.225
更新日期:2017-06-01 00:00:00
abstract::The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.574
更新日期:2015-01-22 00:00:00
abstract::Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03255-6
更新日期:2020-12-06 00:00:00
abstract::Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.445
更新日期:2013-11-07 00:00:00
abstract::Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 and suppresses gene expression by catalyzing histone H3 methylation on lysine 27. EZH2 is overexpressed in metastatic prostate cancer and has been shown to promote cell proliferation and metastasis. Here we show that EZH2 ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.454
更新日期:2014-10-23 00:00:00
abstract::In Slavic folklore, Koschei the Immortal was bony, thin and lean. Was his condition caused by severe calorie restriction (CR)? CR deactivates the target of rapamycin pathway and slows down aging. But the life-extending effect of severe CR is limited by starvation. What if Koschei's anti-aging formula included rapamyci...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.520
更新日期:2014-12-04 00:00:00
abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.344
更新日期:2014-08-21 00:00:00
abstract::The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' com...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.156
更新日期:2014-04-24 00:00:00
abstract::One of the significant challenges for chemotherapy is the appearance of resistance to compounds. Although several signaling pathways have been implicated in the development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain unknown. The present study attempted to illus...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2573-2
更新日期:2020-05-13 00:00:00
abstract::It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CS...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.379
更新日期:2017-10-19 00:00:00
abstract::Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02848-5
更新日期:2020-08-12 00:00:00
abstract::Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of the immune system to ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.183
更新日期:2014-05-15 00:00:00
abstract::Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.501
更新日期:2017-10-05 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::The development of prostate cancer (PCa) from androgen-deprivation therapy (ADT) sensitive to castration resistant (CRPC) seriously impacts life quality and survival of PCa patients. Emerging evidence shows that long noncoding RNAs (lncRNAs) play vital roles in cancer initiation and progression. However, the inherited...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02856-5
更新日期:2020-08-15 00:00:00
abstract::Protein-coding genes account for only ~2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs). A growing volume of literature has proposed that lncRNAs are important factors in cancer. Colon cancer-associated transcript-1 (CCAT1), an lncRNA, which ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.541
更新日期:2015-01-08 00:00:00
abstract::Aggregatibacter (Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative bacterium associated with severe forms of periodontitis. A leukotoxin, which belongs to the repeats-in-toxin family, is believed to be one of its virulence factors and to have an important role in the bacterium's pathogenic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.6
更新日期:2011-03-10 00:00:00
abstract::The NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome is a multi-protein complex, aimed at producing IL-1β in response to danger signals which must be tightly regulated. Here we investigated the importance of the stress sensor, Heat Shock Protein 70 (HSP70) on NLRP3 inflammasome activation. H...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1491-7
更新日期:2019-03-15 00:00:00
abstract::Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinosta...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.306
更新日期:2013-09-12 00:00:00
abstract::The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.32
更新日期:2014-02-27 00:00:00
abstract::Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (Mn...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.20
更新日期:2013-02-21 00:00:00
abstract::Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of N...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.132
更新日期:2017-03-23 00:00:00
abstract::The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0284-8
更新日期:2018-02-14 00:00:00
abstract::We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.52
更新日期:2013-03-07 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0804-6
更新日期:2018-07-03 00:00:00