Abstract：
:High levels of VEGF and leptin are strongly linked to worse prognosis of breast cancer. Leptin signalling upregulates VEGF in human and mouse mammary tumor cells (MT), but the specific molecular mechanisms are largely unknown. Pharmacologic and genetic approaches were used to dissect the mechanism of leptin regulation of VEGF protein and mRNA in MT (4T1, EMT6 and MMT). A series of VEGF-promoter Luc-reporters (full-length and transcription factor-binding deletions) were transfected into MT to analyze leptin regulation of VEGF transcription. Deletion analysis of VEGF promoter and RNA knockdown shows that HIF-1alpha and NFkappaB are essentials for leptin regulation of VEGF. Leptin activation of HIF-1alpha was mainly linked to canonic (MAPK, PI-3K) and non-canonic (PKC, JNK and p38 MAP) signalling pathways. Leptin non-canonic signalling pathways (JNK, p38 MAP and to less extent PKC) were linked to NFkappaB activation. SP1 was involved in leptin regulation of VEGF in 4T1 cells. AP1 was not involved and AP2 repressed leptin-induced increase of VEGF. Overall, these data suggest that leptin signalling regulates VEGF mainly through HIF-1alpha and NFkappaB. These results delineate a comprehensive mechanism for leptin regulation of VEGF in MT. Disruption of leptin signalling could be used as a novel way to treat breast cancer.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Gonzalez-Perez RR,Xu Y,Guo S,Watters A,Zhou W,Leibovich SJdoi
10.1016/j.cellsig.2010.05.003subject
Has Abstractpub_date
2010-09-01 00:00:00pages
1350-62issue
9eissn
0898-6568issn
1873-3913pii
S0898-6568(10)00121-Xjournal_volume
22pub_type
杂志文章abstract：:The orthologous proteins of the stress-activated protein kinase-interacting 1 (Sin1) family have been implicated in several different signal transduction pathways. In this study, we have investigated the function of the full-length human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is produced b...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2004.10.015
更新日期：2005-06-01 00:00:00
abstract：:Reduced connexin43 (Cx43) expression is frequently detected in different types of human cancer. Cx43 has been shown to regulate cancer cell migration in a cell-type dependent manner. In both primary and recurrent human ovarian cancer, overexpression of TGF-β ligand and its receptors have been detected. TGF-β can regul...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.07.010
更新日期：2015-10-01 00:00:00
abstract：:Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Behçet's syndrome. In March 2014, the US Food and Drug Administration approved apremilast for the treatment of adult patien...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.05.014
更新日期：2014-09-01 00:00:00
abstract：:Platelet-activating factor (PAF) is a potent phospholipid mediator involved in several diseases such as allergic asthma, atherosclerosis and psoriasis. The human PAF receptor (PAFR) is a member of the G-protein-coupled receptor family. Following stimulation, PAFR becomes rapidly desensitized; this refractory state is ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2007.05.015
更新日期：2007-10-01 00:00:00
abstract：:Synthesis and degradation of lipids in mammalian adipocytes are tightly and coordinatedly regulated by insulin, fatty acids, reactive oxygen species and drugs. Conversely, the lipogenic or lipolytic state of adipocytes is communicated to other tissues by the secretion of soluble adipocytokines. Here we report that ins...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.10.021
更新日期：2009-02-01 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
abstract：:Labelling with [3H]glucosamine was used to prepare a transforming growth factor-beta 1 (TGF-beta 1)-sensitive glycosylphosphatidylinositol (GPI) from monolayer cultures of rabbit articular chondrocytes (RAC), which may be involved in control of the cell cycle. The polar headgroup of this glycosylphosphatidylinositol w...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(94)90074-4
更新日期：1994-02-01 00:00:00
abstract：:The combination of curcumin and TRAIL and their role in enhancing apoptotic cell death has been reported by many studies. However, the exact molecular mechanism of apoptosis mediated by curcumin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is not yet completely understood. In this study, we obse...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.03.009
更新日期：2012-07-01 00:00:00
abstract：BACKGROUND:Our previous study showed that human omental adipose-derived stem cells (ADSCs) promote ovarian cancer growth and metastasis. In this study, the role of autophagy in the ovarian cancer-promoting effects of omental ADSCs was further determined. METHODS:The growth and invasion of ovarian cancer cells were det...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2020.109549
更新日期：2020-05-01 00:00:00
abstract：:Zfra is a small size 31-amino-acid C2H2 zinc finger-like protein, which is known to interact with c-Jun N-terminal kinase 1 (JNK1), WW domain-containing oxidoreductase (WWOX, FOR or WOX1), TNF receptor-associated death domain protein (TRADD) and nuclear factor kappaB (NF-kappaB) during stress response. Here, we show t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.02.018
更新日期：2008-07-01 00:00:00
abstract：:Neutrophils are key effector cells of the innate immune system, serving as a first line of defense in the response to injury and playing essential roles in the wound healing process. Following myocardial infarction (MI), neutrophils infiltrate into the infarct region to propagate inflammation and begin the initial pha...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109816
更新日期：2021-01-01 00:00:00
abstract：:Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase gene family that contributes to the invasiveness and metastasis in tumor progression. However, the role of LOXL2 in cellular signaling is incompletely understood. In this study, we investigated a possible mechanism of LOXL2 function in tumor metastases in v...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.05.010
更新日期：2014-09-01 00:00:00
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 ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.08.001
更新日期：2011-12-01 00:00:00
abstract：:Rho GTPases are molecular switches involved in the regulation of many cellular processes. This review summarizes work examining how stimulation of receptor tyrosine kinases (RTKs) leads to the activation of Rho guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. The collective findings strongly...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2006.01.022
更新日期：2006-11-01 00:00:00
abstract：:The Rho family of GTPases consists of several small proteins that have been described as molecular switches, playing important roles in a wide variety of fundamental cellular processes and in human diseases such as cancer. These proteins, active in the GTP conformation and inactive in the GDP form, are in turn regulat...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2013.11.034
更新日期：2014-03-01 00:00:00
abstract：:Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR, in estrogen receptor-α (ERα) expressing breast cancer cells, transiently activates ERK downstream of FAK, Src family kinases, and H-Ras. Herein, we show that when uPAR is over-expressed, in two separate ERα-positive breast cancer cell lines, ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.05.011
更新日期：2012-09-01 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：: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：:Interferon-α (IFNα) has enormous potential for anti-proliferative and anti-viral treatments. However, clinical success is still hampered due to its limited bioavailability and thus, lack of sustained modulation of disease-relevant protective programs. Consequently, we here examined whether IFNα immobilized on nanoscal...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.01.012
更新日期：2013-04-01 00:00:00
abstract：:Protein kinase C and the annexins appear to share some unusual and potentially important membrane- and calcium-binding properties. While these proteins are calcium response elements, they are not calcium-binding proteins in the formal sense; at intracellular calcium concentrations, they only bind significant amounts o...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/0898-6568(93)90075-w
更新日期：1993-07-01 00:00:00
abstract：:Cytidine monophosphate kinase (CMPK), a member of the nucleoside monophosphate kinase family, plays an important role in the biosynthesis of nucleoside metabolism, DNA repair and tumour development. In this study, we demonstrated for the first time that CMPK was overexpressed in human ovarian epithelial borderline and...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2017.04.009
更新日期：2017-07-01 00:00:00
abstract：:Induction of nitrosative stress has been observed in various cancer types and in tumor environment. However, it is still unclear how cancer cells combat the effect of nitrosative stress. The main targets of nitrosative stress in cells are cellular lipids, proteins and DNA. Autophagy or self-cleaning generates energy f...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.109411
更新日期：2019-12-01 00:00:00
abstract：:Our previous oligonucleotide array studies revealed that ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL) express high levels of the disheveled proteins (Dvls), a family of proteins that is integral to the Wnt signaling pathways. In this study, we assessed whether the Dvls are important in the pathogenesis of ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2012.09.027
更新日期：2013-01-01 00:00:00
abstract：:Rho guanosine triphosphatases (GTPases) are a family of small proteins which function as molecular switches in a variety of signaling pathways following stimulation of cell surface receptors. RhoGTPases regulate numerous cellular processes including cytoskeleton organization, gene transcription, cell proliferation, mi...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2010.10.022
更新日期：2011-06-01 00:00:00
abstract：:Netrin-1 attracts or repels growing axons during development. The UNC5 receptors mediate the repulsive response, either alone or in complex with DCC receptors. The signaling mechanisms activated by UNC5 are poorly understood. Here, we examined the role of Rho GTPases in UNC5a signaling. We found that UNC5a induced neu...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.09.004
更新日期：2009-12-01 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that can regulate various physiological and pathological processes. The expression of S1P has been detected in human follicular fluid. In addition, two S1P receptors, S1P1 and S1P3, are expressed at a high level in human granulosa cells. Cyclooxygenase-2 (COX-2...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2016.03.006
更新日期：2016-06-01 00:00:00
abstract：:Small ubiquitin-like modifier (SUMO) 2 is a small protein that controls the activity and stability of other proteins by SUMOylation. In this study, T cell-specific SUMO2 overexpressing transgenic mice were generated to study the effect of SUMO2 on T lymphocytes. SUMO2 overexpression promoted differentiation of interle...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.03.001
更新日期：2015-06-01 00:00:00
abstract：:Cell cycle progression from G2 phase into mitosis is regulated by a complex network of mechanisms, all of which finally control the timing of Cyclin B/CDK1 activation. PLK1 regulates a network of events that contribute to regulating G2/M phase progression. Here we have used a proteomics approach to identify proteins t...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.08.009
更新日期：2015-11-01 00:00:00
abstract：:Understanding receptor activation is important for disease intervention. Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal tumors. To better understand the regulation of activation, we studied the two c-KIT ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.07.011
更新日期：2013-11-01 00:00:00
abstract：:Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative multifactorial disease characterized, like other diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or frontotemporal dementia (FTD), by the degeneration of specific neuronal cell populations. Motor neuron loss is distinctive of ALS. However, ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2010.05.016
更新日期：2010-10-01 00:00:00
