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 and survival. Several studies highlighted a critical role for MKK3 in tumor progression and invasion, and we previously identified MKK3 as transcriptional target of mutant (mut) p53 to sustain cell proliferation and survival, thus rendering MKK3 a promising target for anticancer therapies. Here, we found that targeting MKK3 with RNA interference, in both wild-type (wt) and mutp53-carrying cells, induced endoplasmic reticulum stress and autophagy that, respectively, contributed to stabilize wtp53 and degrade mutp53. MKK3 depletion reduced cancer cell proliferation and viability, whereas no significant effects were observed in normal cellular context. Noteworthy, MKK3 depletion in combination with chemotherapeutic agents increased tumor cell response to the drugs, in both wtp53 and mutp53 cancer cells, as demonstrated by enhanced poly (ADP-ribose) polymerase cleavage and reduced clonogenic ability in vitro. In addition, MKK3 depletion reduced tumor growth and improved biological response to chemotherapeutic in vivo. The overall results indicate MKK3 as a novel promising molecular target for the development of more efficient anticancer treatments in both wtp53- and mutp53-carrying tumors.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Baldari S,Ubertini V,Garufi A,D'Orazi G,Bossi Gdoi
10.1038/cddis.2014.591subject
Has Abstractpub_date
2015-01-29 00:00:00pages
e1621issn
2041-4889pii
cddis2014591journal_volume
6pub_type
杂志文章abstract::As an important modality for the local control of colorectal cancer (CRC), radiotherapy or neoadjuvant radiotherapy is widely applied in the clinic, but radioresistance has become a major obstacle for CRC radiotherapy. Here we reported that B7-H3, an important costimulatory molecule, is associated with radioresistance...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03041-4
更新日期:2020-10-03 00:00:00
abstract::G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflam...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0267-9
更新日期:2018-02-14 00:00:00
abstract::Reactive oxygen species (ROS) accumulation are involved in noise- and ototoxic drug-induced hair cell loss, which is the major cause of hearing loss. Bmi1 is a member of the Polycomb protein family and has been reported to regulate mitochondrial function and ROS level in thymocytes and neurons. In this study, we repor...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.549
更新日期:2015-01-22 00:00:00
abstract::ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02912-0
更新日期:2020-08-22 00:00:00
abstract::Diffuse large B cell lymphoma (DLBCL) is a common and fatal hematological malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA biomarker in DLBCL needs to be investigated badly, as well as its function and molecular mechanism. To further explore, mic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1479-3
更新日期:2019-03-15 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::Aneuploidy including trisomy results in developmental disabilities and is the leading cause of miscarriages in humans. Unlike trisomy 21, pathogenic mechanisms of trisomy 18 remain unclear. Here, we successfully generated induced pluripotent stem cells (iPSCs) from human amniotic fluid cells (AFCs) with trisomy 18 pre...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.565
更新日期:2017-10-26 00:00:00
abstract::Long non-coding RNA (lncRNA) plays an important role in the development of human malignant tumours. Recently, an increasing number of lncRNAs have been identified and investigated in a variety of tumours. However, the expression pattern and biological function of lncRNAs in cervical cancer still remain largely unexplo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1228-z
更新日期:2018-12-05 00:00:00
abstract::The vascular leakage in diabetic retinopathy leads to macular edema and vision loss. Although astrocyte play an important role in regulating blood-brain barrier integrity in the brain, the precise role of astrocyte in blood-retinal barrier was yet to be elucidated. This study aimed to investigate the role of angiopoie...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.347
更新日期:2016-02-18 00:00:00
abstract::Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2064-5
更新日期:2019-10-28 00:00:00
abstract::Renal tubular cell death is the key factor of the pathogenesis of ischemia/reperfusion (I/R) kidney injury. Ferroptosis is a type of regulated cell death (RCD) found in various diseases. However, the underlying molecular mechanisms related to ferroptosis in renal I/R injury remain unclear. In the present study, we inv...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03135-z
更新日期:2020-10-28 00:00:00
abstract::Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2248-z
更新日期:2020-01-30 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::Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood. In this study, we aimed to investigate the expression pattern and function roles of SPATS2 i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03039-y
更新日期:2020-10-09 00:00:00
abstract::Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 ass...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.86
更新日期:2010-12-16 00:00:00
abstract::Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.189
更新日期:2016-07-28 00:00:00
abstract::Parkin (Park2), a RING-between-RING-type E3 ubiquitin ligase, has been implicated in regulating NF-κB. Mutations in Parkin are associated with Parkinson's disease. Here we investigated the interaction of Parkin with Receptor-interacting protein kinase 1 (RIPK1) kinase, a key mediator of multiple signaling pathways act...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0770-z
更新日期:2018-06-28 00:00:00
abstract::Many cancer therapies are being developed for the induction of durable anti-tumor immunity, especially for malignant tumors. The activation of antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), can bridge innate and adaptive immune responses against tumors. However, APCs have an immunosu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1459-7
更新日期:2019-03-04 00:00:00
abstract::Synapsin I is a phosphoprotein that coats the cytoplasmic side of synaptic vesicles and regulates their trafficking within nerve terminals. Autoantibodies against Syn I have been described in sera and cerebrospinal fluids of patients with numerous neurological diseases, including limbic encephalitis and clinically iso...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2106-z
更新日期:2019-11-14 00:00:00
abstract::Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.15
更新日期:2013-02-14 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::Cytotoxic T lymphocytes (CTL) and natural killer cells (NK)-mediated elimination of tumor cells is mostly dependent on Granzyme B apoptotic pathway, which is regulated by the wild type (wt) p53 protein. Because TP53 inactivating mutations, frequently found in human tumors, could interfere with Granzyme B-mediated cell...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1950-1
更新日期:2019-09-20 00:00:00
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
更新日期:2020-01-22 00:00:00
abstract::The original version of this article contained an error in the name of one of the co-authors (Kayvan Mohkam). This has been corrected in the PDF and HTML versions. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-020-2262-1
更新日期:2020-01-23 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::The role of T lymphocytes in central nervous system (CNS) injuries is controversial, with inconsistent results reported concerning the effects of T-lymphocyte transfer on spinal cord injury (SCI). Here, we demonstrate that a specific T-lymphocyte subset enhances functional recovery after contusion SCI in mice. Intrape...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.106
更新日期:2012-08-09 00:00:00
abstract::Circular RNAs (circRNAs) have been identified play a vital role in various different types of cancer via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains largely unclear. In this study, we systematically characterized the circRNA expression profiles in the LUAD cancer tissues and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2230-9
更新日期:2020-01-16 00:00:00
abstract::Retinal ganglion cells (RGCs) undergo rapid cell death by apoptosis after injury but can be rescued by suppression of caspase-2 (CASP2) using an siRNA to CASP2 (siCASP2). Pigment epithelium-derived factor (PEDF), has neuroprotective and anti-angiogenic functions and protects RGC from death. The purpose of this study w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1379-6
更新日期:2019-02-04 00:00:00
abstract::Following publication of this article, it was brought to our attention that there was a typo in the References (reference number 43) whereby the first author's name was misspelled. The correct citation is provided below. We apologize for the inconvenience. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-2029-8
更新日期:2019-10-22 00:00:00
abstract::Advanced glycation end products (AGEs) can stimulate osteoblast apoptosis and have a critical role in the pathophysiology of diabetic osteoporosis. Mitochondrial abnormalities are closely related to osteoblast dysfunction. However, it remains unclear whether mitochondrial abnormalities are involved in AGE-induced oste...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0718-3
更新日期:2018-06-04 00:00:00