Abstract:
:In more than 90% of cancers including glioma, telomere elongation reverse transcriptase (hTERT) is overexpressed. In the present study, we sought to explore whether matrix metalloproteinase-9 (MMP-9) shRNA could alter hTERT-mediated proliferation in glioma cells. MMP-9 shRNA induced senescence and apoptosis in glioma cells by inhibiting hTERT expression and telomere activity. MMP-9 silencing decreased oncogenic c-Myc expression (hTERT activator), whereas the expression of the c-Myc antagonist MAD increased drastically (hTERT repressor); both c-Myc and MAD are transcription factors for hTERT. In addition, MMP-9 suppression turns the switch from c-Myc/MAX to MAD/MAX heterodimer binding to the hTERT promoter as determined by chromatin immunoprecipitation assay. We also show that silencing MAD via siRNA restored hTERT expression and inhibited senescence in glioma cells. MMP-9 transcriptional suppression decreased the expression of FAK, phospho FAK and β1 integrin in glioma xenograft cells. Further, MMP-9 suppression decreased the interaction of β1 integrin/FAK and also MMP-9/β1 integrin as confirmed by immunoprecipitation analysis. Studies with either function blocking β1 integrin or FAK shRNA indicate that suppression of MMP-9 decreased β1 integrin-mediated induction of FAK, which led to decreased hTERT expression. Moreover, 4910 and 5310 glioma xenograft tissue sections from mice treated with MMP-9 shRNA showed reduced expression of FAK/c-Myc and elevated MAD levels. Decreased co-localization of β1 integrin and MMP-9 was associated with MMP-9-suppressed tumor sections. Further, immunoprecipitation analysis showed decreased association of proteins involved in telomere end repair in MMP-9 shRNA-treated glioma cells. Elevated levels of p73 and TRAIL and the results of the FACS analysis show induction of apoptosis in MMP-9-silenced glioma cells. Taken together, these data provide new insights into the mechanisms underlying MMP-9-mediated hTERT expression in glioma proliferation.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Ponnala S,Chetty C,Veeravalli KK,Dinh DH,Klopfenstein JD,Rao JSdoi
10.1016/j.cellsig.2011.08.001subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2065-75issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(11)00246-4journal_volume
23pub_type
杂志文章abstract::Perivascular adipocyte (PVAC) biofunctions were closely related to cardiovascular diseases; its specific biological mechanisms remained unclear. How to adjust PVAC functions of vascular cells is an important topic. The present study was designed to investigate whether FAK/Pyk2 and ERK1/2 MAPK signaling pathways partic...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.017
更新日期:2014-12-01 00:00:00
abstract::Protein kinase D3 is a novel member of the serine/threonine kinase family PKD. The regulatory region of PKD contains a tandem repeat of C1 domains designated C1a and C1b that bind diacylglycerol and phorbol esters, and are important membrane targeting modules. Here, we investigate the activities of individual C1 domai...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.02.007
更新日期:2005-11-01 00:00:00
abstract::The activation of corticotrophin-releasing hormone receptor (CRHR) 1 is implicated in neuronal injury in experimental stroke. However, little is known about the relationship between CRHR1 activation and brain endothelial barrier impairment after ischemia and reperfusion (I/R). Recently we have demonstrated that the ac...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109467
更新日期:2020-02-01 00:00:00
abstract::Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.01.010
更新日期:2011-05-01 00:00:00
abstract::The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac hypertrophy is thought to occur through its ability to inhibit the chronic GPCR signaling that promotes pathogenic growth both in vivo and in cultured cardiomyocytes. However, RGS2 is known to have additional functions beyond its activity as...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.006
更新日期:2014-06-01 00:00:00
abstract::Differential regulation of PLC-beta 1 and -beta 2 by the G-protein alpha-subunit, G alpha 11, and by G-protein beta gamma-subunits was studied utilizing recombinant PLC-beta 1 and -beta 2. Rat PLC-beta 1 and human PLC-beta 2 were purified after recombinant baculovirus-mediated expression in Sf9 cells. The catalytic pr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(95)00039-r
更新日期:1995-09-01 00:00:00
abstract::High affinity Ins(1,4,5)P3-binding sites of permeabilized hepatocytes are probably the ligand recognition sites of the receptors that mediate the effects of Ins(1,4,5)P3 on intracellular Ca2+ mobilization. We have now solubilized these sites from rat liver membranes in the zwitterionic detergent, CHAPS, and shown that...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(91)90037-u
更新日期:1991-01-01 00:00:00
abstract::Signal transducers and activators of transcription 3 (STAT3) is reported to regulate cell proliferation, survival, and differentiation, and thus plays a central role in development and carcinogenesis. Accumulating evidence demonstrated the involvement of cellular Src (c-Src) tyrosine kinase in the activation of STAT3....
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109762
更新日期:2020-11-01 00:00:00
abstract::The mammalian target of rapamycin complex 1(mTORC1) integrates diverse signals to control cell growth, proliferation, survival, and metabolism. Role of reactive oxygen species (ROS) on mTORC1 signaling remains obscure and mechanisms through which ROS modulate mTORC1 are not known.We demonstrate that low doses ROS expo...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.05.015
更新日期:2010-10-01 00:00:00
abstract::The induction of cytolytic activity in PC60, a murine T-cell hybridoma, is paralleled by a rise in the level of BLT-esterase (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl esterase), a serine esterase specific for activated T-cells. Both interleukin-1 (IL-1) and dibutyryl cAMP were albe to increase the esterase activi...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90045-c
更新日期:1990-01-01 00:00:00
abstract::The inwardly rectifying K+ channels of the GIRK (Kir3) family, members of the superfamily of inwardly rectifying K+ channels (Kir), are important physiological tools to regulate excitability in heart and brain by neurotransmitters, and the only ion channels conclusively shown to be activated by a direct interaction wi...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/s0898-6568(97)00095-8
更新日期:1997-12-01 00:00:00
abstract::Transforming growth factor-β1 (TGF-β1) regulates the tissue response to injury and is the principal driver of excessive scarring leading to fibrosis and eventual organ failure. The TGF-β1 effectors SMAD3 and p53 are major contributors to disease progression. While SMAD3 is an established pro-fibrotic factor, the role ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.02.017
更新日期:2014-07-01 00:00:00
abstract::The human ether-a-go-go related gene (HERG) potassium channel has elicited intense scientific interest due to its role in cardiac repolarization and its association with arrhythmia and sudden cardiac death. Increasing evidence indicates the involvement of HERG channels in the pathophysiology of cancer. In the present ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.010
更新日期:2010-01-01 00:00:00
abstract::The nuclear factor kappa B (NF-κB) transcription factor-mediated transcription is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli. Both the proteolytic and non-proteolytic functions of ubiquitination are critically important for the regulation of NF-κB activation. L...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.11.017
更新日期:2011-04-01 00:00:00
abstract::Signal transducer and activator of transcription 1 (STAT1) is an important mediator for cytokine signal transduction, particularly IFN-γ. Following IFN-γ stimulation, STAT1 is activated through tyrosine phosphorylation. Little is known about the function and regulation of STAT1 dephosphorylation after activation. We s...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.04.003
更新日期:2011-08-01 00:00:00
abstract::S6K1, a critical downstream substrate of mTORC1, has been implicated in regulating protein synthesis and a variety of processes that impinge upon cell growth and proliferation. While the role of the cytoplasmic p70(S6K1) isoform in the regulation of translation has been intensively studied, the targets and function of...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.016
更新日期:2011-08-01 00:00:00
abstract::Insulin is an inducer of brown fat adipogenesis through the activation of a signalling network that involves positive/negative modulators. Given the importance of brown adipose tissue (BAT) for basal thermogenic energy expenditure, we investigated the role of PTP1B in the acquisition of terminal differentiated phenoty...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.11.019
更新日期:2010-04-01 00:00:00
abstract::Follistatin-like 1 (FSTL1) functions as a pivotal modulator of inflammation and is implicated in many inflammatory diseases such as rheumatoid arthritis. Here, we report that FSTL1 is strongly upregulated and secreted during osteoclast differentiation of bone marrow-derived macrophages (BMMs) and that FSTL1 positively...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.05.018
更新日期:2016-09-01 00:00:00
abstract::Recent global incidences and mortality rates have placed colorectal cancer (CRC) at third and second positions, respectively, among both sexes of all ages. Resistance during chemotherapy is a big problem in the treatment and disease-free survival of CRC patients. Discovery of new anticancer drug(s) is a time taking pr...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109803
更新日期:2020-12-01 00:00:00
abstract::The present study was designed to investigate (i) the role of AMPK activation in inducing autophagy in androgen-dependent prostate cancer cells subjected to androgen deprivation and hypoxia, and (ii) whether autophagy offers a survival advantage under these harsh conditions. Low androgen and low oxygen are two co-exis...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.04.008
更新日期:2011-09-01 00:00:00
abstract::Understanding the underlying mechanism by which cancer cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into tumor recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 breast cancer cells i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.01.011
更新日期:2017-02-01 00:00:00
abstract::CD45 is a leukocyte specific transmembrane glycoprotein and a receptor-like protein tyrosine phosphatase (PTP). CD45 can be expressed as several alternatively spliced isoforms that differ in the extracellular domain. The isoforms are regulated in a cell type and activation state-dependent manner, yet their function ha...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2009.10.003
更新日期:2010-03-01 00:00:00
abstract::Phospholipase D (PLD) is involved in diverse cellular processes including cell movement, adhesion, and vesicle trafficking through cytoskeletal rearrangements. However, the mechanism by which PLD induces cytoskeletal reorganization is still not fully understood. Here, we describe a new link to cytoskeletal changes tha...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.014
更新日期:2011-08-01 00:00:00
abstract::Long-term amino acid starvation represents a form of metabolic stress which stimulates gene expression. Here we report that depriving HeLa cells for any one of a series of amino acids activates c-Jun N-terminal kinase-1 (JNK-1). In contrast, the other mitogen-activated protein kinases (MAPKs) ERK-1 and, to a lesser ex...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(01)00159-0
更新日期:2001-06-01 00:00:00
abstract::Five G protein-coupled receptors (GPCRs) for the lysophospholipid sphingosine 1-phosphate (S1P) have been cloned and characterized so far. We report here about the identification of gpr3, gpr6 and gpr12 as additional members of the S1P-GPCR family. When expressed transiently in HEK293 cells, gpr3, gpr6 and gpr12 confe...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(02)00041-4
更新日期:2002-11-01 00:00:00
abstract::Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.030
更新日期:2010-01-01 00:00:00
abstract::Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in vivo. In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis. However, little is known on the expression patter...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2016.01.007
更新日期:2016-07-01 00:00:00
abstract::Prostaglandin D2 (PGD2) stimulated the formation of choline in a dose-dependent manner in the range between 10 nM and 10 microM. The effect of PGD2 on the formation of inositol phosphates (EC50 was 20 nM) was more potent than that on the formation of choline (EC50 was 0.5 microM). The formation of choline stimulated b...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)00059-k
更新日期:1995-01-01 00:00:00
abstract::AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, is known to be activated during T cell activation. T cell activation by T cell receptor (TCR) engagement or its pharmacological mimics, PMA plus ionomycin (PMA/Io), induces immunomodulatory FasL and cyclooxygenase-2 (COX-2) expression. ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.01.015
更新日期:2012-06-01 00:00:00
abstract::Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality with varied defects in organ development. To understand the underlying molecular mechanisms of the...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.11.010
更新日期:2019-02-01 00:00:00