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 and apoptosis in human cervical carcinoma HeLa cells, both responses being abrogated by Bcl-x(L) overexpression. We synthesized a number of new fluorescent edelfosine analogs, which preserved the proapoptotic activity of the parent drug, and colocalized with mitochondria in HeLa cells. Edelfosine induced swelling in isolated mitochondria, indicating an increase in mitochondrial membrane permeability. This mitochondrial swelling was independent of reactive oxygen species generation. A structurally related inactive analog was unable to promote mitochondrial swelling, highlighting the importance of edelfosine molecular structure in its effect on mitochondria. Raft disruption inhibited mitochondrial localization of the drug in cells and edelfosine-induced swelling in isolated mitochondria. Edelfosine promoted a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. Our data suggest that direct interaction of edelfosine with mitochondria eventually leads to mitochondrial dysfunction and apoptosis. These observations unveil a new framework in cancer chemotherapy that involves a link between lipid rafts and mitochondria in the mechanism of action of an antitumor drug, thus opening new avenues for cancer treatment.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
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 Cdoi
10.1038/cddis.2011.41subject
Has Abstractpub_date
2011-05-19 00:00:00pages
e158issn
2041-4889pii
cddis201141journal_volume
2pub_type
杂志文章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::Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and functio...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.51
更新日期:2016-03-17 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::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::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::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::Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that U...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1170-0
更新日期:2018-11-21 00:00:00
abstract::p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The p63 gene has different transcriptional start sites, which generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.175
更新日期:2013-05-23 00:00:00
abstract::Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1894-5
更新日期:2019-09-09 00:00:00
abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1354-2
更新日期:2019-02-12 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::Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SS...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02756-8
更新日期:2020-07-18 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.74
更新日期:2011-08-11 00:00:00
abstract::Intrinsic apoptosis relies on the ability of the BCL-2 family to induce the formation of pores on the outer mitochondrial membrane. Previous studies have shown that both BAX and BAK are essential during murine embryogenesis, and reports in human cancer cell lines identified non-canonical roles for BAX and BAK in mitoc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03002-x
更新日期:2020-09-25 00:00:00
abstract::Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocyte...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.230
更新日期:2014-05-22 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::Interleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased ce...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2627-5
更新日期:2020-05-29 00:00:00
abstract::Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enz...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.388
更新日期:2013-10-24 00:00:00
abstract::Enhanced SNHG1 (small nucleolar RNA host gene 1) expression has been found to play a critical role in the initiation and progression of hepatocellular carcinoma (HCC) with its detailed mechanism largely unknown. In this study, we show that SNHG1 promotes the HCC progression through epigenetically silencing CDKN1A and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03031-6
更新日期:2020-10-02 00:00:00
abstract::The subversion of the normal function exerted by the cellular prion protein (PrP(C)) in neurons by pathogenic prions is assumed to have a central role in the pathogenesis of transmissible spongiform encephalopathies. Using two murine models of prion infection, the 1C11 neuronal cell line and neurospheres, we document ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.195
更新日期:2013-01-10 00:00:00
abstract::Gastric cancer (GC) ranks among the top five malignant tumors worldwide by the incidence and mortality rate. However, the mechanisms underlying its progression are poorly understood. In this study, we investigated the role of SIRT1, a class III deacetylase, in the invasion and metastasis of GC. Here, we found that kno...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1033-8
更新日期:2018-09-24 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::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1373-z
更新日期:2019-03-07 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::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::Elongation factor Tu GTP binding domain containing 2 (EFTUD2), a spliceosomal GTPase, plays a pivotal role in multiple organ development and innate immune. It has been reported that EFTUD2 is a new host factor with activity against HCV infection. However, the role of EFTUD2 in solid tumors, including hepatocellular ca...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03040-5
更新日期:2020-10-06 00:00:00
abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1481-9
更新日期:2019-03-11 00:00:00
abstract::In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0578-x
更新日期:2018-06-04 00:00:00
abstract::Drug resistance is one of the major hurdles for cancer treatment. However, the underlying mechanisms are still largely unknown and therapeutic options remain limited. In this study, we show that microRNA (miR)-587 confers resistance to 5-fluorouracil (5-FU)-induced apoptosis in vitro and reduces the potency of 5-FU in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.200
更新日期:2015-08-06 00:00:00
abstract::Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.67
更新日期:2010-10-21 00:00:00