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 correlates with higher tumor grade and stage, and platinum resistance. Herein we show that TRAP1 is often deleted in high-grade serous OC patients (N=579), and that TRAP1 expression is correlated with the copy number, suggesting this could be one of the driving mechanisms for the loss of TRAP1 expression in OC. At molecular level, downregulation of TRAP1 associates with higher expression of p70S6K, a kinase frequently active in OC with emerging roles in cell migration and tumor metastasis. Indeed, TRAP1 silencing in different OC cells induces upregulation of p70S6K expression and activity, enhancement of cell motility and epithelial-mesenchymal transition (EMT). Consistently, in a large cohort of OC patients, TRAP1 expression is reduced in tumor metastases and directly correlates with the epithelial marker E-Cadherin, whereas it inversely correlates with the transcription factor Slug and the matrix metallopeptidases 2 and 9. Strikingly, pharmacological inhibition of p70S6K reverts the high motility phenotype of TRAP1 knock-down cells. However, although p70S6K inhibition or silencing reduces the expression of the transcription factors Snail and Slug, thus inducing upregulation of E-Cadherin expression, it is unable to revert EMT induced by TRAP1 silencing; furthermore, p70S6K did not show any significant correlation with EMT genes in patients, nor with overall survival or tumor stage, suggesting an independent and predominant role for TRAP1 in OC progression. Altogether, these results may provide novel approaches in OC with reduced TRAP1 expression, which could be resistant to therapeutic strategies based on the inhibition of the p70S6K pathway, with potential future intervention in OC invasion and metastasis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Amoroso MR,Matassa DS,Agliarulo I,Avolio R,Lu H,Sisinni L,Lettini G,Gabra H,Landriscina M,Esposito Fdoi
10.1038/cddis.2016.400subject
Has Abstractpub_date
2016-12-15 00:00:00pages
e2522issue
12issn
2041-4889pii
cddis2016400journal_volume
7pub_type
杂志文章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::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::Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dys...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03075-8
更新日期:2020-10-10 00:00:00
abstract::Correction to: NPG Asia Materials (2018) https://doi.org/10.1038/s41427-018-0014-9 published online on 16 April 2018. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0639-1
更新日期:2018-05-24 00:00:00
abstract::The rapid, typically all-or-none process of mitochondrial outer membrane permeabilization (MOMP) constitutes a primary cell death decision that is controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP decisions are governed by and emanate from the dynamic interplay of pro- and antiapoptotic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0464-6
更新日期:2018-04-01 00:00:00
abstract::Human pluripotent stem cells provide a versatile platform for regenerative studies, drug testing and disease modeling. That the expression of only four transcription factors, Oct4, Klf4, Sox2 and c-Myc (OKSM), is sufficient for generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells has ...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2015.167
更新日期:2015-07-23 00:00:00
abstract::The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protei...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.561
更新日期:2015-01-15 00:00:00
abstract::Hypertension-induced cardiac hypertrophy and attenuated cardiac function are the major characteristics of early stage heart failure. Cardiomyocyte death in pathological cardiac conditions is the primary cause of heart failure and mortality. Our previous studies found that heat shock factor 1 (HSF1) protected cardiomyo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.320
更新日期:2017-08-10 00:00:00
abstract::B-cell lymphoma-2 (Bcl-2) proteins mediate intrinsic-, or mitochondrial-, initiated apoptosis. We have investigated the structure and function of the least characterized Bcl-2 family member, Bcl-B, solving the crystal structure of a Bcl-B:Bim complex to 1.9 Å resolution. Bcl-B is distinguished from other Bcl-2 family ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.178
更新日期:2012-12-13 00:00:00
abstract::The oncogenic human papillomavirus (HPV) E6/E7 proteins are essential for the onset and maintenance of HPV-associated malignancies. Here, we report that activation of the cellular ubiquitin-proteasome system (UPS) by the omega-3 fatty acid, docosahexaenoic acid (DHA), leads to proteasome-mediated degradation of E6/E7 ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.477
更新日期:2014-11-13 00:00:00
abstract::Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression l...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.399
更新日期:2016-01-21 00:00:00
abstract::Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis due to early invasion and metastasis. However, the molecular mechanisms through which GBC cells interact with the tumor microenvironment (TME) remain poorly understood. Here, we examined the role of the tumor suppressor apoptosis-stimu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1145-1
更新日期:2018-11-02 00:00:00
abstract::Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in si...
journal_title:Cell death & disease
pub_type: 临床试验,杂志文章
doi:10.1038/cddis.2014.256
更新日期:2014-06-26 00:00:00
abstract::Despite the introduction of novel targeted therapies, chemotherapy still remains the primary treatment for metastatic melanoma in poorly funded healthcare environments or in case of disease relapse, with no reliable molecular markers for progression-free survival (PFS) available. As chemotherapy primarily eliminates c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2309-3
更新日期:2020-02-13 00:00:00
abstract::Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viab...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.144
更新日期:2016-05-26 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::Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-s...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.248
更新日期:2013-07-11 00:00:00
abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0508-y
更新日期:2018-05-01 00:00:00
abstract::Methamphetamine (METH), a commonly used controlled substance, is known to exacerbate neuropathological dysfunction in HIV-infected individuals. The neuropathological manifestation results from cell death or dysfunction in the central nervous system (CNS) wherein autophagy is expected to have an important role. Autopha...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.317
更新日期:2016-10-20 00:00:00
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
更新日期:2014-03-27 00:00:00
abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.298
更新日期:2015-12-03 00:00:00
abstract::The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were establishe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1898-1
更新日期:2019-09-10 00:00:00
abstract::Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03054-z
更新日期:2020-10-14 00:00:00
abstract::Melatonin, an endogenous hormone molecule, has a variety of biological functions, but a functional role of melatonin in the infection of Gram-negative bacterium Vibrio vulnificus has yet to be described. In this study, we investigated the molecular mechanism of melatonin in the apoptosis of human intestinal epithelial...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0083-7
更新日期:2018-01-19 00:00:00
abstract::Sponges of the porifera family harbor some of the evolutionary most ancient orthologs of the B-cell lymphoma-2 (Bcl-2) family, a protein family critical to regulation of apoptosis. The genome of the sponge Geodia cydonium contains the putative pro-survival Bcl-2 homolog BHP2, which protects sponge tissue as well as ma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.469
更新日期:2017-01-12 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::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::Extracorporeal photochemotherapy (ECP) is employed for the management of cutaneous T cell lymphoma (CTCL). ECP involves the extracorporeal exposure of white blood cells (WBCs) to a photosensitizer, 8-methoxypsoralen (8-MOP), in the context of ultraviolet A (UVA) radiation, followed by WBC reinfusion. Historically, the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1819-3
更新日期:2019-08-02 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival. It is urgent to search for new efficient drugs with good stability and safety for clinical therapy. This study aims to identify potential anticancer drugs from a compound library consisting of 429 natural products....
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2730-7
更新日期:2020-07-13 00:00:00
abstract::Bevacizumab in neoadjuvant therapy provides a new hope of improved survival for patients with triple-negative breast cancer (TNBC) by targeting vascular endothelial growth factor in combination with chemotherapy, but curative effect is limited by bevacizumab's continuous use while mechanisms remain incompletely unders...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03161-x
更新日期:2020-11-19 00:00:00