Abstract:
:Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate microenvironmental components by reshaping them into accomplices of metastasis. Recent studies have identified a plethora of new molecular and cellular modulators of metastasis that have dynamic or even opposite roles, dominating the phenotypic plasticity of both tumoral and microenvironmental components. In this review we discuss their bipotential functions and the possible underpinning mechanisms, as well as their implications for targeted cancer therapy.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Zhuang X,Zhang H,Hu Gdoi
10.1016/j.tips.2019.04.005subject
Has Abstractpub_date
2019-06-01 00:00:00pages
419-429issue
6eissn
0165-6147issn
1873-3735pii
S0165-6147(19)30080-Xjournal_volume
40pub_type
杂志文章,评审abstract::G-protein-coupled receptors (GPCRs) are dynamically regulated by various mechanisms that tune their response to external stimuli. Modulation of their plasma membrane density, via trafficking between subcellular compartments, constitutes an important process in this context. Substantial information has been accumulated...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2008.07.009
更新日期:2008-10-01 00:00:00
abstract::Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2007.02.009
更新日期:2007-04-01 00:00:00
abstract::Influenza A viral infections claim millions of lives worldwide and continue to impose a major burden on healthcare systems. Current pharmacological strategies to control influenza A virus-induced lung disease are problematic owing to antiviral resistance and the requirement for strain-specific vaccination. The product...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2011.09.001
更新日期:2012-01-01 00:00:00
abstract::Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.05.006
更新日期:2017-08-01 00:00:00
abstract::Drugs of abuse are very powerful reinforcers, and even in conditions of limited access (where the organism is not dependent) these drugs will motivate high rates of operant responding. This presumed hedonic property and the drugs' neuropharmacological specificity provide a means of studying the neuropharmacology and n...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(92)90060-j
更新日期:1992-05-01 00:00:00
abstract::Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(90)90009-w
更新日期:1990-07-01 00:00:00
abstract::Within five years of discovering endothelin (ET-1) in 1988, the first report of an orally available ET receptor antagonist was published. Within twelve years, bosentan, the first ET receptor antagonist to gain marketing authorization, was made available for the treatment of pulmonary artery hypertension (PAH). Since t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.10.002
更新日期:2007-11-01 00:00:00
abstract::Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.06.001
更新日期:2018-08-01 00:00:00
abstract::It has taken 17 years from the first identification of a voltage-gated Ca2+ channel (CaV) beta-subunit as a band on a gel following purification of skeletal muscle dihydropyridine (DHP) receptors in 1987 to the publication of key information on the structures of Ca2+ channel beta-subunits. Three recent X-ray crystallo...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.10.008
更新日期:2004-12-01 00:00:00
abstract::Pathogenic granulocytes (eosinophils and neutrophils) infiltrate airway tissues in asthma and chronic obstructive pulmonary disease. Granulocytes release tissue-toxic and inflammatory mediators, making their removal an important pharmacological goal. Removal is thought to be accomplished through apoptosis followed by ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2006.07.006
更新日期:2006-09-01 00:00:00
abstract::Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.04.008
更新日期:2005-07-01 00:00:00
abstract::Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.05.007
更新日期:2006-07-01 00:00:00
abstract::Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easil...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2016.10.014
更新日期:2017-02-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insig...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.11.009
更新日期:2018-02-01 00:00:00
abstract::Parkinson's disease (PD) is a progressive neurodegenerative disorder. Although therapies that treat the symptoms of the disease have proven efficacy, strategies that slow or stop the neurodegenerative process are currently not available. Recently, the National Institute of Neurological Disorders and Stroke (NINDS) con...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2004.03.003
更新日期:2004-05-01 00:00:00
abstract::Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01249-8
更新日期:1998-10-01 00:00:00
abstract::Cyclic AMP (cAMP) steers the generation of basal heart beat in the sinoatrial node. It also induces sinoatrial tachycardia and increased cardiac force, elicited through activation of Gs-protein-coupled receptors (GsPCRs). Phosphodiesterases (PDEs) hydrolyse cAMP. In the heart mainly PDE3 and PDE4 would be expected to ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2011.03.003
更新日期:2011-07-01 00:00:00
abstract::Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.01.006
更新日期:2007-03-01 00:00:00
abstract::Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) home...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2010.08.007
更新日期:2010-12-01 00:00:00
abstract::A diet low in carbohydrates helps to reduce the amount of ingested calories and to maintain a healthy weight. With this in mind, food and beverage companies have reformulated a large number of their products, replacing sugar or high fructose corn syrup with several different types of zero-calorie sweeteners to decreas...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2011.06.007
更新日期:2011-11-01 00:00:00
abstract::The broad importance of receptor-activated phosphoinositide hydrolysis in the physiological action of hormones, neurotransmitters and growth factors has sparked interest in the study of transmembrane signalling events responsible for activation of phospholipase C. As with receptors involved in regulation of adenylyl c...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90008-4
更新日期:1989-09-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) are involved in almost every (patho)physiological process, which explains their importance as drug targets. GPCRs have long been regarded as on/off-switches, which is reflected by direct activation or blockade of these receptors through the majority of marketed GPCR drugs. In recent...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2014.10.002
更新日期:2014-12-01 00:00:00
abstract::For more than 30 years, WNT/β-catenin and planar cell polarity signaling has formed the basis for what we understand to be the primary output of the interaction between WNTs and their cognate receptors known as Frizzleds (FZDs). In the shadow of these pathways, evidence for the involvement of heterotrimeric G proteins...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.07.001
更新日期:2018-09-01 00:00:00
abstract::The hypothalamic neuropeptide oxytocin (OT) has attracted the attention both of the scientific community and a general audience because of its prosocial effects in mammals, and OT is now seen as a facilitator of mammalian species propagation. Furthermore, OT is a candidate for the treatment of social deficits in sever...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2017.08.005
更新日期:2017-11-01 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.10.001
更新日期:2016-01-01 00:00:00
abstract::HIV-1 integrase (IN) executes the insertion of proviral DNA into the host cell genome, an essential step in the retroviral life cycle. This is a multi-step process that starts in the cytosol and culminates in the nucleus of the infected cell. It is becoming increasingly clear that IN interacts with a wide range of dif...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.09.005
更新日期:2007-10-01 00:00:00
abstract::Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis. Anti-leukotriene therapy has proven benefits in the treatment of respiratory disease, either through the inhibition of leukotriene synthesis or the se...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.11.006
更新日期:2008-02-01 00:00:00
abstract::Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.06.009
更新日期:2007-08-01 00:00:00
abstract::The concept that receptors can exist in multiple conformational states is becoming a physical reality. A fundamental question is how many active states need to be proposed in order to account for pharmacological observations, in particular, the finding that the same receptor type can exhibit a different agonist pharma...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01105-x
更新日期:1997-10-01 00:00:00
abstract::Since the cloning and expression of many of the G protein-coupled receptors during the 1980s, there has been a massive increase in our understanding of many aspects of their function. The use of molecular biology to engineer and express mutant receptors has made it possible to determine key amino acids involved in rec...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(98)01231-0
更新日期:1998-08-01 00:00:00