Abstract:
:Anaplastic Thyroid Cancer (ATC) is an aggressive malignancy with limited therapeutic options and dismal patient survival. We have previously shown MADD to be differentially overexpressed in multiple cancer histologies and to contribute to tumor cell growth and survival. Therefore, we targeted MADD by gene silencing, explored its effect on cellular proliferation and metastases and examined its therapeutic potential in an orthotopic ATC model in athymic nude mice. When compared to untreated control and scramble siRNA, MADD siRNA treatment inhibited the proliferative capacity of 8505C, C643 and HTH7 cells in vitro and 8505C-derived-orthotopic tumor growth in vivo. MADD ablation caused a significant reduction in cellular migration and invasion potential; clonogenic capacity; as well as, mitochondrial length and potential in vitro. This MADD siRNA-induced anti-migratory/invasive effect corresponded with inhibition of epithelial-mesenchymal transition (EMT) and Wnt signaling. Mechanistically, MADD siRNA inhibited TNFα induced activation of pERK, pGSK3β and β-catenin, suggesting that MADD knockdown might exert its anti-migratory/invasive effects, by blocking TNFα/ERK/GSK3β axis. MADD siRNA can inhibit β-catenin nuclear translocation and consequently, the expression of its target genes in ATC cells. In in vivo experiments, along with tumor regression, MADD siRNA treatment also decreased evidence of lung metastases. Immunohistochemically, MADD siRNA-treated tumor tissues exhibited a reduction in Ki67 and N-Cadherin expression, and an increase in E-Cadherin expression. In conclusion, we show the crucial role of MADD in ATC tumorigenesis and metastasis and its potential implications as a molecular target for ATC therapy.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Saini S,Sripada L,Tulla K,Kumar P,Yue F,Kunda N,Maker AV,Prabhakar BSdoi
10.1038/s41419-019-1351-5subject
Has Abstractpub_date
2019-02-13 00:00:00pages
145issue
2issn
2041-4889pii
10.1038/s41419-019-1351-5journal_volume
10pub_type
杂志文章abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.391
更新日期:2014-10-02 00:00:00
abstract::Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2326-2
更新日期:2020-02-18 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::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::Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.11
更新日期:2014-02-13 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::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02821-2
更新日期:2020-08-18 00:00:00
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
更新日期:2014-09-04 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::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
abstract::Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1446-z
更新日期:2019-02-25 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::MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression by binding to the three untranslated regions of their target mRNAs. Deregulations of miRs were shown to play pivotal roles in tumorigenesis and progression. Recent research efforts have been devoted to translating these basic discoverie...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.270
更新日期:2014-07-17 00:00:00
abstract::Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.65
更新日期:2012-06-21 00:00:00
abstract::The mechanism of pathological osteogenesis in Ankylosing spondylitis (AS) is largely unknown. Our previous studies demonstrated that the imbalance between BMP-2 and Noggin secretion induces abnormal osteogenic differentiation of marrow-derived mesenchymal stem cells (MSCs) from AS patients in a two-dimensional culture...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1586-1
更新日期:2019-04-25 00:00:00
abstract::Glucocorticoids (GCs) represent an important component of modern treatment regimens for fludarabine-refractory or TP53-defective chronic lymphocytic leukemia (CLL). However, GC therapy is not effective in all patients. The molecular mechanisms responsible for GC-induced apoptosis and resistance were therefore investig...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.102
更新日期:2012-08-16 00:00:00
abstract::Histamine is a widely distributed biogenic amine involved in the regulation of an array of biological processes. Serum histamine level is markedly elevated in the early stages of acute myocardial infarction, whereas the role it plays remains unclear. Histidine decarboxylase (HDC) is the unique enzyme responsible for h...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0723-6
更新日期:2018-06-07 00:00:00
abstract::Mammalian folliculogenesis is a complex process in which primordial follicles develop into pre-ovulatory follicles, followed by ovulation to release mature oocytes. In this study, we explored the role of miR-144 in ovulation. miR-144 was one of the differentially expressed microRNAs, which showed 5.59-fold changes, in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.24
更新日期:2017-02-09 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells associated with chronic infection by human T-cell lymphotropic virus type-1 (HTLV-1). ATLL patients with aggressive subtypes have dismal outcomes. We demonstrate that ATLL cells co-opt an early checkpoint within the tumor necrosis factor receptor ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2294-6
更新日期:2020-02-05 00:00:00
abstract::Acute lung injury (ALI) is a pulmonary disorder, which can result in fibrosis of the lung tissues. Recently, mesenchymal stem cell (MSC) has become a novel therapeutic method for ALI. However, the potential mechanism by which MSC regulates the progression of ALI remains blurry. The present study focused on investigati...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03034-3
更新日期:2020-10-15 00:00:00
abstract::Aberrantly expressed miRNAs play a crucial role in the development of multiple cancer types, including chordoma. However, the detailed molecular mechanisms are unclear and need to be elucidated. In this study, miRNAs were screened by miRNA array analysis and then confirmed by real-time PCR analysis. We found that miR-...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0738-z
更新日期:2018-06-07 00:00:00
abstract::Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.381
更新日期:2017-08-17 00:00:00
abstract::The intestinal epithelial monolayer, at the boundary between microbes and the host immune system, plays an important role in the development of inflammatory bowel disease (IBD), particularly as a target and producer of pro-inflammatory TNF. Chronic overexpression of TNF leads to IBD-like pathology over time, but the m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1275-5
更新日期:2019-02-06 00:00:00
abstract::Cell migration plays pivotal roles in many biological processes; however, its underlying mechanism remains unclear. Here, we find that NudC-like protein 2 (NudCL2), a cochaperone of heat shock protein 90 (Hsp90), modulates cell migration by stabilizing both myosin-9 and lissencephaly protein 1 (LIS1). Either knockdown...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02739-9
更新日期:2020-07-14 00:00:00
abstract::Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.41
更新日期:2014-02-27 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::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...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0804-6
更新日期:2018-07-03 00:00:00
abstract::Estrogen receptor-alpha positive (ER(+)) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER(+) mammary luminal tumors arising in Tip30(-/-)MMTV-Neu mice exhibited increased enrichment of lumina...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.224
更新日期:2014-05-22 00:00:00
abstract::Senescence is an antiproliferative mechanism that can suppress tumor development and can be induced by oncogenes such as genes of the Ras family. Although studies have implicated bioactive sphingolipids (SL) in senescence, the specific mechanisms remain unclear. Here, using MCF10A mammary epithelial cells, we demonstr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03281-4
更新日期:2021-01-04 00:00:00
abstract::The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is diffic...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.431
更新日期:2013-10-31 00:00:00