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 multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins. ZLDI-8 treatment enhanced the susceptibility of HCC cells to a small molecular kinase inhibitor Sorafenib, and chemotherapy agents Etoposide and Paclitaxel. ZLDI-8 treatment enhanced the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model. These results suggest that ZLDI-8 can be a promising therapeutic agent to enhance Sorafenib's anti-tumor effect and to overcome the MDR of HCC patients.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Zhang Y,Li D,Jiang Q,Cao S,Sun H,Chai Y,Li X,Ren T,Yang R,Feng F,Li BA,Zhao Qdoi
10.1038/s41419-018-0804-6subject
Has Abstractpub_date
2018-07-03 00:00:00pages
743issue
7issn
2041-4889pii
10.1038/s41419-018-0804-6journal_volume
9pub_type
杂志文章abstract::Procaspase-3-activating compound 1 (PAC-1) induces procaspase-3 activation via zinc chelation. However, whether PAC-1 employs other mechanisms remains unknown. Here we systematically screened for potent PAC-1 targets using 29 enhanced green fluorescent protein-labeled reporter cell lines and identified hypoxia-inducib...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1038-3
更新日期:2018-10-04 00:00:00
abstract::The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0843-z
更新日期:2018-07-23 00:00:00
abstract::Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Sin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.529
更新日期:2014-12-11 00:00:00
abstract::TAF6δ is a pro-apoptotic splice variant of the RNA polymerase II general transcription factor, TAF6, that can dictate life vs. death decisions in animal cells. TAF6δ stands out from classical pro-apoptotic proteins because it is encoded by a gene that is essential at the cellular level, and because it functions as a c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0115-3
更新日期:2018-01-22 00:00:00
abstract::Apoptotic cysteine-aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.54
更新日期:2010-09-23 00:00:00
abstract::Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related death worldwide and a high medical need for more effective therapies. Small-molecule inhibitors of the bromodomain and extra terminal domain (BET) family such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer types...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.271
更新日期:2016-09-08 00:00:00
abstract::Hippo signaling plays critical roles in intestinal regeneration. However, the mechanisms which regulate its activity in vivo are largely unknown. We hypothesize that protease-activated receptor 2 (PAR2) signaling, which could be activated by trypsin, might affect YAP activity in the setting of tissue damage and regene...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0995-x
更新日期:2018-09-20 00:00:00
abstract::Dia1, which belongs to the diaphanous-related formin family, influences a variety of cellular processes through straight actin elongation activity. Recently, novel DIA1 mutants such as p.R1213X (p.R1204X) and p.A265S, have been reported to cause an autosomal dominant sensorineural hearing loss (DFNA1). Additionally, a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02743-z
更新日期:2020-07-16 00:00:00
abstract::Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies throu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.199
更新日期:2013-07-18 00:00:00
abstract::Activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) has been implicated in diverse kidney diseases, yet its in vivo significance in diabetic nephropathy (DN) is largely unknown. In the present study, we demonstrated a podocyte-specific Rac1-deficient mouse strain and showed that specific inhibition of Rac1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0353-z
更新日期:2018-03-01 00:00:00
abstract::The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.139
更新日期:2012-10-11 00:00:00
abstract::MicroRNAs (miRNAs) deregulation is frequent in human gastric cancers (GCs), but the role of specific miRNAs involved in this disease remains elusive. MiR-22 was previously reported to act as tumor suppressors or oncogenes in diverse cancers. However, their accurate expression, function and mechanism in GC are largely ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.297
更新日期:2015-11-26 00:00:00
abstract::Patients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell deat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2081-4
更新日期:2019-11-07 00:00:00
abstract::The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients' survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) sp...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02970-4
更新日期:2020-11-02 00:00:00
abstract::Mitogen-activated protein kinase kinase 3 (MAP2K3, MKK3) is a member of the dual specificity protein kinase group that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic or stress-inducing stimuli and participates in the MAP kinase-mediated signaling cascade, leading to cell proliferation a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.591
更新日期:2015-01-29 00:00:00
abstract::Breast cancer is the worldwide leading cause of cancer mortality in women. The majority of deaths from breast cancer arise from metastasis of local tumors. Cancer cells support their rapid proliferation by diverting metabolites into anabolic pathways, but during cancer metastasis, the proliferative program of invasive...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.27
更新日期:2016-03-24 00:00:00
abstract::Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastogr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.554
更新日期:2017-10-26 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::Growing evidence indicates that cell adhesion to extracellular matrix (ECM) plays an important role in cancer chemoresistance. Leukemic T cells express several adhesion receptors of the β1 integrin subfamily with which they interact with ECM. However, the role of β1 integrins in chemoresistance of T-cell acute lymphob...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1593-2
更新日期:2019-05-01 00:00:00
abstract::Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to dat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0348-9
更新日期:2018-02-22 00:00:00
abstract::We sought to identify miRNAs that can efficiently induce apoptosis in ovarian cancer cells by overcoming BCL-X(L) and MCL1 anti-apoptotic activity, using combined computational and experimental approaches. We found that miR-491-5p efficiently induces apoptosis in IGROV1-R10 cells by directly inhibiting BCL-X(L) expres...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.389
更新日期:2014-10-09 00:00:00
abstract::A cell-in-cell process refers to the invasion of one living cell into another homotypic or heterotypic cell. Different from non-apoptotic death processes of internalized cells termed entosis or cannibalism, we previously reported an apoptotic cell-in-cell death occurring during heterotypic cell-in-cell formation. In t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.352
更新日期:2013-10-10 00:00:00
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
更新日期:2017-07-27 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::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::Mitochondrial apoptosis-inducing factor (AIF) influences the oxidative phosphorylation (OXPHOS) system and can be recruited as a mediator of cell death. Pathogenic mutations in the AIFM1 gene cause severe human diseases. Clinical manifestations include inherited peripheral neuropathies, prenatal cerebral abnormalities...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.170
更新日期:2015-07-09 00:00:00
abstract::Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.10
更新日期:2010-04-01 00:00:00
abstract::The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 suppo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.532
更新日期:2014-01-23 00:00:00
abstract::Phenothiazines are a family of heterocyclic compounds whose clinical utility includes treatment of psychiatric disorders as well as chemotherapy-induced emesis. Various studies have demonstrated that these compounds possess cytotoxic activities in tumor cell lines of different origin. However, there is considerable co...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.56
更新日期:2014-03-13 00:00:00
abstract::Alzheimer's disease (AD) is pathologically characterised by the age-dependent deposition of β-amyloid (Aβ) in senile plaques, intraneuronal accumulation of tau as neurofibrillary tangles, synaptic dysfunction and neuronal death. Neuroinflammation, typified by the accumulation of activated microglia and reactive astroc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.50
更新日期:2011-06-02 00:00:00