当前位置： SCI文献检索 > Cell Death & Disease期刊下所有文献 > Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme.

Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme.

Abstract：

:Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality. We report that NIM811, a small molecule cyclophilin-binding inhibitor, induces catastrophic vacuolization and cell death in GBM cells. These unique features are distinct from many known cell death pathways, and are associated with an incompletely defined cell death mechanism known as paraptosis. We found that NIM811-induced paraptosis is due to unresolved ER stress. The abnormal upregulation of protein translation was responsible for the build-up of misfolded or unfolded proteins in ER, whereas pro-survival autophagy and UPR signals were shutdown during prolonged treatment with NIM811. Although cycloheximide has been claimed to suppress paraptosis, instead we find that it only temporarily delayed vacuole formation, but actually enhanced paraptotic cell death in the long term. On the other hand, mTOR inhibitors rescued cells from NIM811-induced paraptosis by sustaining autophagy and the UPR, while specifically restraining cap-dependent translation. These findings not only provide new insights into the mechanisms underlying paraptosis, but also shed light on a potential approach to enhance GBM treatment.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang L,Gundelach JH,Bram RJ

doi

10.1038/cddis.2017.217

subject

Has Abstract

pub_date

2017-05-18 00:00:00

pages

e2807

issue

5

issn

2041-4889

pii

cddis2017217

journal_volume

8

pub_type

杂志文章

相关文献

Cell Death & Disease文献大全
  • MicroRNA-153-5p promotes the proliferation and metastasis of renal cell carcinoma via direct targeting of AGO1.

    abstract：:MicroRNAs (miRNAs) have been demonstrated to affect the biological processes of cancers and showed great potential for prognostic biomarkers. In this study, we screened differentially expressed miRNAs in ccRCC based on three dimensions of metastasis, prognosis, and differential expression compared to normal tissue usi...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-020-03306-y

    authors： Li Z,Zhao S,Zhu S,Fan Y

    更新日期：2021-01-04 00:00:00

  • Adenanthin targets peroxiredoxin I/II to kill hepatocellular carcinoma cells.

    abstract：:Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs ...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2014.345

    authors： Hou JK,Huang Y,He W,Yan ZW,Fan L,Liu MH,Xiao WL,Sun HD,Chen GQ

    更新日期：2014-09-04 00:00:00

  • MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression.

    abstract：:Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a ...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2014.485

    authors： Jeong BC,Kang IH,Hwang YC,Kim SH,Koh JT

    更新日期：2014-11-20 00:00:00

  • Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis.

    abstract：:Long noncoding RNAs (lncRNAs) have been identified as potential prognostic tools and therapeutic biomarkers for a variety of human cancers. However, the functional roles and underlying mechanisms of key lncRNAs affecting laryngeal squamous cell carcinomas (LSCCs) are largely unknown. Here, we adopted a novel subpathwa...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-020-2581-2

    authors： Li X,Xu F,Meng Q,Gong N,Teng Z,Xu R,Zhao M,Xia M

    更新日期：2020-06-18 00:00:00

  • Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling.

    abstract：:BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes pla...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-017-0230-1

    authors： Zhao HJ,Klausen C,Li Y,Zhu H,Wang YL,Leung PCK

    更新日期：2018-02-07 00:00:00

  • Inhibition of autophagy increased AGE/ROS-mediated apoptosis in mesangial cells.

    abstract：:The aim of our study was to investigate the role of autophagy, a homeostatic process involved in the lysosomal degradation of damaged cell organelles and proteins, in regulating the survival of mesangial cells treated with advanced glycation end products (AGEs). In the present study, AGEs induced mitochondrial depolar...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2016.322

    authors： Xu L,Fan Q,Wang X,Zhao X,Wang L

    更新日期：2016-11-03 00:00:00

  • eIF2α signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice.

    abstract：:Bone loss in postmenopausal osteoporosis is induced chiefly by an imbalance of bone-forming osteoblasts and bone-resorbing osteoclasts. Salubrinal is a synthetic compound that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylation of eIF2α alleviates endoplasmic reticu...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-019-2159-z

    authors： Li J,Li X,Liu D,Hamamura K,Wan Q,Na S,Yokota H,Zhang P

    更新日期：2019-12-04 00:00:00

  • Circular RNA FAM114A2 suppresses progression of bladder cancer via regulating ∆NP63 by sponging miR-762.

    abstract：:Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens an...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-020-2226-5

    authors： Liu T,Lu Q,Liu J,Xie S,Feng B,Zhu W,Liu M,Liu Y,Zhou X,Sun W,Zhang Y,Chen X,Fang F,Guo H,Yang R

    更新日期：2020-01-22 00:00:00

  • Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia.

    abstract：:Extremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the pre...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-019-1763-2

    authors： Zhang Z,Zhang L,Zhou Y,Li L,Zhao J,Qin W,Jin Z,Liu W

    更新日期：2019-07-18 00:00:00

  • Metabolic and molecular insights into an essential role of nicotinamide phosphoribosyltransferase.

    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

    authors： Zhang LQ,Van Haandel L,Xiong M,Huang P,Heruth DP,Bi C,Gaedigk R,Jiang X,Li DY,Wyckoff G,Grigoryev DN,Gao L,Li L,Wu M,Leeder JS,Ye SQ

    更新日期：2017-03-23 00:00:00

  • Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p.

    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

    authors： Ma MZ,Chu BF,Zhang Y,Weng MZ,Qin YY,Gong W,Quan ZW

    更新日期：2015-01-08 00:00:00

  • Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance.

    abstract：:Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2014.509

    authors： Dahan P,Martinez Gala J,Delmas C,Monferran S,Malric L,Zentkowski D,Lubrano V,Toulas C,Cohen-Jonathan Moyal E,Lemarie A

    更新日期：2014-11-27 00:00:00

  • Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity.

    abstract：:Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133(pos) and...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2012.93

    authors： Akunuru S,James Zhai Q,Zheng Y

    更新日期：2012-07-19 00:00:00

  • Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis.

    abstract：:Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main cell type of extracellular matrix (ECM) deposition during hepatic fibrosis. Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been reported, but the functional roles and mechanisms of DNA methylation in hepatic fib...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-018-1032-9

    authors： Chen X,Li WX,Chen Y,Li XF,Li HD,Huang HM,Bu FT,Pan XY,Yang Y,Huang C,Meng XM,Li J

    更新日期：2018-10-03 00:00:00

  • Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury.

    abstract：:Phosphatase and tensin homolog (PTEN) regulates apoptosis and axonal growth in the developing and adult central nervous system (CNS). Here, we show that human PTEN C-terminal PDZ interactions play a critical role in neuronal apoptosis and axon regeneration after traumatic CNS injury and stroke, highlighted by the find...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-019-1802-z

    authors： Shabanzadeh AP,D'Onofrio PM,Magharious M,Choi KAB,Monnier PP,Koeberle PD

    更新日期：2019-07-29 00:00:00

  • MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus.

    abstract：:Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-018-0628-4

    authors： Godfrey JD,Morton JP,Wilczynska A,Sansom OJ,Bushell MD

    更新日期：2018-05-29 00:00:00

  • socs7, a target gene of microRNA-145, regulates interferon-β induction through STAT3 nuclear translocation in bladder cancer cells.

    abstract：:We recently reported that microRNA (miR)-145 is downregulated and induces apoptosis in human bladder cancer cells. Also, it is suggested that the ectopic expression of miR-145 induces apoptosis with the induction of TRAIL expression in several cancer cells. Here, we demonstrated a novel mechanism of apoptosis inductio...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2013.11

    authors： Noguchi S,Yamada N,Kumazaki M,Yasui Y,Iwasaki J,Naito S,Akao Y

    更新日期：2013-02-07 00:00:00

  • Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers.

    abstract：:Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2014.112

    authors： Sheth A,Escobar-Alvarez S,Gardner J,Ran L,Heaney ML,Scheinberg DA

    更新日期：2014-03-27 00:00:00

  • miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer.

    abstract：:Colorectal cancer (CRC) is the second major cause of tumor-related deaths. MicroRNAs (miRNAs) have pivotal roles in CRC progression. Here, we describe the effect of miR-181d on CRC cell metabolism and underlying molecular mechanism. Our data firmly demonstrated that knockdown of miR-181d suppressed CRC cell proliferat...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2017.300

    authors： Guo X,Zhu Y,Hong X,Zhang M,Qiu X,Wang Z,Qi Z,Hong X

    更新日期：2017-07-27 00:00:00

  • MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro.

    abstract：:Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-020-2367-6

    authors： Yadav SK,Kambis TN,Kar S,Park SY,Mishra PK

    更新日期：2020-03-13 00:00:00

  • Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant.

    abstract：:Colorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cancer cells often resist chemotherapy by evading apoptosis. Antagonists of an inhibitor of apoptosis proteins (IAPs) can restore defective a...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-020-03232-z

    authors： Fichtner M,Bozkurt E,Salvucci M,McCann C,McAllister KA,Halang L,Düssmann H,Kinsella S,Crawford N,Sessler T,Longley DB,Prehn JHM

    更新日期：2020-11-30 00:00:00

  • Salt-inducible kinase 1 regulates bone anabolism via the CRTC1-CREB-Id1 axis.

    abstract：:New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-019-1915-4

    authors： Kim MK,Kwon JO,Song MK,Kim B,Kim H,Lee ZH,Koo SH,Kim HH

    更新日期：2019-10-31 00:00:00

  • The SGK3-triggered ubiquitin-proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex.

    abstract：:Podocyte damage is commonly accompanied by destabilization of the podocalyxin (PC)/ezrin complex. Serum- and glucocorticoid-inducible kinase 3 (SGK3) plays a role in the maintenance of podocyte function, but the details of this role are poorly understood. Herein we demonstrated that SGK3 and its downstream target prot...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-018-1161-1

    authors： Yuan YP,Zhao H,Peng LQ,Li ZF,Liu S,Yuan CY,Mwamunyi MJ,Pearce D,Yao LJ

    更新日期：2018-11-01 00:00:00

  • A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium.

    abstract：:Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobu...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2014.437

    authors： Di Angelantonio S,Murana E,Cocco S,Scala F,Bertollini C,Molinari MG,Lauro C,Bregestovski P,Limatola C,Ragozzino D

    更新日期：2014-10-30 00:00:00

  • TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial-mesenchymal transition.

    abstract：:Ovarian cancer (OC) is the second leading cause of gynecological cancer death worldwide. Although the list of biomarkers is still growing, molecular mechanisms involved in OC development and progression remain elusive. We recently demonstrated that lower expression of the molecular chaperone TRAP1 in OC patients corre...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2016.400

    authors： Amoroso MR,Matassa DS,Agliarulo I,Avolio R,Lu H,Sisinni L,Lettini G,Gabra H,Landriscina M,Esposito F

    更新日期：2016-12-15 00:00:00

  • A multi-omic analysis reveals the role of fumarate in regulating the virulence of enterohemorrhagic Escherichia coli.

    abstract：:The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infecti...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-018-0423-2

    authors： Kuo CJ,Wang ST,Lin CM,Chiu HC,Huang CR,Lee DY,Chang GD,Chou TC,Chen JW,Chen CS

    更新日期：2018-03-07 00:00:00

  • Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria.

    abstract：:Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2011.41

    authors： Mollinedo F,Fernández M,Hornillos V,Delgado J,Amat-Guerri F,Acuña AU,Nieto-Miguel T,Villa-Pulgarín JA,González-García C,Ceña V,Gajate C

    更新日期：2011-05-19 00:00:00

  • Monoglyceride lipase gene knockout in mice leads to increased incidence of lung adenocarcinoma.

    abstract：:Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/s41419-017-0188-z

    authors： Liu R,Wang X,Curtiss C,Landas S,Rong R,Sheikh MS,Huang Y

    更新日期：2018-01-18 00:00:00

  • Correction: Mechanism of Snhg8/miR-384/Hoxa13/FAM3A axis regulating neuronal apoptosis in ischemic mice model.

    abstract：:Following the publication of this article, the authors realized there was an error in Figure 6H in which two versions of the figure appear.This does not impact the conclusions of the article. ...

    journal_title：Cell death & disease

    pub_type： 已发布勘误

    doi：10.1038/s41419-019-1865-x

    authors： Liu J,An P,Xue Y,Che D,Liu X,Zheng J,Liu Y,Yang C,Li Z,Yu B

    更新日期：2019-08-21 00:00:00

  • IGFBP-rP1 suppresses epithelial-mesenchymal transition and metastasis in colorectal cancer.

    abstract：:Epithelial-mesenchymal transition (EMT) was initially recognized during organogenesis and has recently been reported to be involved in promoting cancer invasion and metastasis. Cooperation of transforming growth factor-β (TGF-β) and other signaling pathways, such as Ras and Wnt, is essential to inducing EMT, but the m...

    journal_title：Cell death & disease

    pub_type： 杂志文章

    doi：10.1038/cddis.2015.59

    authors： Zhu S,Zhang J,Xu F,Xu E,Ruan W,Ma Y,Huang Q,Lai M

    更新日期：2015-03-19 00:00:00