Abstract:
:The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role in cell invasion and cancer metastasis, and the mechanism underlying the process are still unclear. Here we found that TSP50 overexpression greatly promoted cell migration, invasion, adhesion and formation of the stellate structures in 3D culture system in vitro as well as lung metastasis in vivo. Conversely, TSP50 knockdown caused the opposite changes. Mechanistic studies revealed that NF-κB signaling pathway was required for TSP50-induced cell migration and metastasis, and further results indicated that TSP50 overexpression enhanced expression and secretion of MMP9, a target gene of NF-κB signaling. In addition, knockdown of MMP9 resulted in inhibition of cell migration and invasion in vitro and lung metastasis in vivo. Most importantly, immunohistochemical staining of human breast cancer samples strongly showed that the coexpression of TSP50 and p65 as well as TSP50 and MMP9 were correlated with increased metastasis and poor survival. Furthermore, we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status. Taken together, this work identified the TSP50 activation of MMP9 as a novel signaling mechanism underlying human breast cancer invasion and metastasis.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Song ZB,Ni JS,Wu P,Bao YL,Liu T,Li M,Fan C,Zhang WJ,Sun LG,Huang YX,Li YXdoi
10.1038/cddis.2015.61subject
Has Abstractpub_date
2015-03-26 00:00:00pages
e1703issn
2041-4889pii
cddis201561journal_volume
6pub_type
杂志文章abstract::New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1915-4
更新日期:2019-10-31 00:00:00
abstract::We reported previously that adult (HRAS-/-; NRAS-/-) double knockout (DKO) mice showed no obvious external phenotype although lower-than-expected numbers of weaned DKO animals were consistently tallied after crossing NRAS-KO and HRAS-KO mice kept on mixed genetic backgrounds. Using mouse strains kept on pure C57Bl/6 b...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2075-2
更新日期:2019-11-04 00:00:00
abstract::Cardiac glycosides (CGs), prescribed to treat cardiovascular alterations, display potent anti-cancer activities. Despite their well-established target, the sodium/potassium (Na(+)/K(+))-ATPase, downstream mechanisms remain poorly elucidated. UNBS1450 is a hemi-synthetic cardenolide derived from 2″-oxovorusharin extrac...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.134
更新日期:2015-06-11 00:00:00
abstract::Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.21
更新日期:2017-02-02 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::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::Pathological retinal neovascularization is the most common cause of vision loss. PKCθ has been shown to play a role in type 2 diabetes, which is linked to retinal neovascularization. Based on these clues, we have studied the role of PKCθ and its downstream target genes JunB and VEGFR3 in retinal neovascularization usi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2522-0
更新日期:2020-05-07 00:00:00
abstract::Epidemiology studies indicate that consumption of high-fat diet (HFD) is directly associated with the development of colorectal cancer (CRC). However, the exact component in HFD and the mechanism underlying its effect on CRC growth remained unclear. Our study shows that HFD feeding increases β2AR expression in the xen...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1958-6
更新日期:2019-09-26 00:00:00
abstract::Altered mitochondrial metabolism acts as an initial cause for cardiovascular diseases and metabolic intermediate succinate emerges as a mediator of mitochondrial dysfunction. This work aims to investigate whether or not extracellular succinate accumulation and its targeted G protein-coupled receptor-91 (GPR91) activat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0708-5
更新日期:2018-06-04 00:00:00
abstract::We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.52
更新日期:2013-03-07 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-2189-6
更新日期:2020-01-06 00:00:00
abstract::Global cerebral ischemia/reperfusion (I/R) facilitates the activation of procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have remained uncharacterized. Protein S-nitrosylation and denitrosylation is an important reversible posttranslational modification, which is a common mechanism in signal tra...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.299
更新日期:2013-08-15 00:00:00
abstract::Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was re...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03043-2
更新日期:2020-10-22 00:00:00
abstract::Tumor metastasis leads to high mortality; therefore, understanding the mechanisms that underlie tumor metastasis is crucial. Generally seen as a secretory protein, osteopontin (OPN) is involved in multifarious pathophysiological events. Here, we present a novel pro-metastatic role of OPN during metastatic colonization...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.422
更新日期:2016-12-29 00:00:00
abstract::The incidence of malignant melanoma has continued to rise during the past decades. However, in the last few years, treatment protocols have significantly been improved thanks to a better understanding of the key oncogenes and signaling pathways involved in its pathogenesis and progression. Anticancer therapy would eit...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-017-0059-7
更新日期:2018-01-25 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::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03185-3
更新日期:2020-11-12 00:00:00
abstract::A proper number of oligodendrocytes in the nerve system is essential for neuronal functions. In the olfactory bulb (OB), enriched oligodendrocytes are crucial for olfactory information processing. However, how the precise number of oligodendrocytes in the OB is regulated remains elusive. Here we identified that the tr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03371-3
更新日期:2021-01-18 00:00:00
abstract::Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.509
更新日期:2014-11-27 00:00:00
abstract::The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX wo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.108
更新日期:2017-03-16 00:00:00
abstract::Colorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cancer cells often resist chemotherapy by evading apoptosis. Antagonists of an inhibitor of apoptosis proteins (IAPs) can restore defective a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03232-z
更新日期:2020-11-30 00:00:00
abstract::Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by dopaminergic neuronal loss that initiates in the substantia nigra pars compacta and by the formation of intracellular inclusions mainly constituted by aberrant α-synuclein (α-syn) deposits known as Lewy bodies. Most cases ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2092-1
更新日期:2019-11-12 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::Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-assoc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02915-x
更新日期:2020-08-26 00:00:00
abstract::The clinical use of the antineoplastic drug cisplatin is limited by its deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to renal cell death and irreversible kidney dysfunction. Oxidative stress could be modified by the cystic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.355
更新日期:2013-10-03 00:00:00
abstract::Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast canc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0417-0
更新日期:2018-03-07 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::Breast cancer is the leading cause of cancer-related death in women worldwide. Human epidermal growth factor receptor 2 (HER2)-positive subtype comprises 20% of sporadic breast cancers and is an aggressive disease. While targeted therapies have greatly improved its management, primary and acquired resistance remain a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-021-03414-3
更新日期:2021-01-26 00:00:00
abstract::Induction of lethal autophagy has become a strategy to eliminate glioma cells, but it remains elusive whether autophagy contributes to cell death via causing mitochondria damage and nuclear translocation of apoptosis inducing factor (AIF). In this study, we find that silibinin induces AIF translocation from mitochondr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02866-3
更新日期:2020-08-14 00:00:00
abstract::Our previous study demonstrated that angiogenesis increased during the recovery of heat-denatured endothelial cells. However, the mechanism is still unclear. This study aimed to investigate the relation of autophagy and angiogenesis during the recovery of heat-denatured endothelial cells. A rat deep partial-thickness ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1194-5
更新日期:2018-11-19 00:00:00