Abstract：
:Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for growth and development of cells. Sphingosine kinase (SPHK) is an important regulator for keeping this balance. It controls the level of S1P and plays important roles in proliferation, migration, and invasion of cancer cells and tumor angiogenesis. There are two isoenzymes of sphingosine kinase, SPHK1 and SPHK2. SPHK1 is ubiquitously expressed in most cancers where it promotes survival and proliferation, while SPHK2 is restricted to only certain tissues and its functions are not well characterized. SPHK1 is currently considered as a novel target for the treatment of cancers. Targeting SPHK1 would provide new strategies for cancer treatment and improve the prognosis of cancer patients. Here we review and summarize the current research findings on the SPHK1-S1P axis in cancer from many aspects including structure, expression, regulation, mechanism, and potential inhibitors.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Zheng X,Li W,Ren L,Liu J,Pang X,Chen X,Kang,Wang J,Du Gdoi
10.1016/j.pharmthera.2018.10.011subject
Has Abstractpub_date
2019-03-01 00:00:00pages
85-99eissn
0163-7258issn
1879-016Xpii
S0163-7258(18)30195-5journal_volume
195pub_type
杂志文章,评审abstract：:Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somatoautonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs such as cisplatin is associated with an increase in the co...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00057-3
更新日期：2003-08-01 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through de...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.01.003
更新日期：2008-04-01 00:00:00
abstract：:G protein-gated inwardly rectifying potassium channels (Kir3/GirK) are important for maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Coupled to numerous G protein-coupled receptors (GPCRs), they mediate the effects of many neurotransmitters, neuromodulators and hormones cont...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2021.107808
更新日期：2021-01-18 00:00:00
abstract：:Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), periphe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.08.005
更新日期：2006-01-01 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in the human genome that respond to a plethora of signals, including neurotransmitters, peptide hormones, and odorants, to name a few. They couple to second messenger signaling cascade mechanisms via heterotrimeric G-proteins. R...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00160-7
更新日期：2001-11-01 00:00:00
abstract：:The nuclear transport proteins, importins and exportins (karyopherin-β proteins), may play an important role in cancer by transporting key mediators of oncogenesis across the nuclear membrane in cancer cells. During nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators during the processin...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.020
更新日期：2016-08-01 00:00:00
abstract：:Enhancing the effects of endogenously-released cannabinoid ligands in the brain might provide therapeutic effects more safely and effectively than administering drugs that act directly at the cannabinoid receptor. Inhibitors of fatty acid amide hydrolase (FAAH) prevent the breakdown of endogenous ligands for cannabino...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.01.003
更新日期：2013-04-01 00:00:00
abstract：:Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.04.002
更新日期：2011-07-01 00:00:00
abstract：:Cyclooxygenase (COX) enzymes, or prostaglandin-endoperoxide synthases (PTGS), are heme-containing bis-oxygenases that catalyze the first committed reaction in metabolism of arachidonic acid (AA) to the potent lipid mediators, prostanoids and thromboxanes. Two isozymes of COX enzymes (COX-1 and COX-2) have been identif...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.04.011
更新日期：2006-11-01 00:00:00
abstract：:RSV infection of the lower respiratory tract in infants is the leading cause of pediatric hospitalizations and second to malaria in causing infant deaths worldwide. RSV also causes substantial morbidity in immunocompromised and elderly populations. The only available therapeutic is a prophylactic drug called Palivizum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107712
更新日期：2020-10-27 00:00:00
abstract：:Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are a class of lipid-lowering medications, with a major activity on plasma cholesterol levels, now enjoying a vast popularity among physicians and patients. These drugs, affecting a very early and key step of sterol biosynthesis, differ to a large extent ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90031-8
更新日期：1993-12-01 00:00:00
abstract：:Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.01.007
更新日期：2018-06-01 00:00:00
abstract：:During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation-a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-ves...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.10.001
更新日期：2017-03-01 00:00:00
abstract：:Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.08.002
更新日期：2018-02-01 00:00:00
abstract：:Neurosteroids are neuroactive brain-born steroids. They can act through non-genomic and/or through genomic pathways. Genomic pathways are largely described for steroid hormones: the binding to nuclear receptors leads to transcription regulation. Pregnenolone, Dehydroepiandrosterone, their respective sulfate esters and...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.06.011
更新日期：2018-11-01 00:00:00
abstract：:Aspirin is integral to the secondary prevention of cardiovascular disease and acts to impair the development of platelet-mediated atherothromboembolic events by irreversible inhibition of platelet cyclooxygenase-1 (COX-1). Inhibition of this enzyme prevents the synthesis of the potent pro-aggregatory prostanoid thromb...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.08.005
更新日期：2014-01-01 00:00:00
abstract：:Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00021-1
更新日期：1997-01-01 00:00:00
abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00110-1
更新日期：1997-10-01 00:00:00
abstract：:Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.05.013
更新日期：2014-11-01 00:00:00
abstract：:Neutrophils form an essential part of innate immunity against infection. Cancer chemotherapy-induced neutropenia (CCIN) is a condition in which the number of neutrophils in a patient's bloodstream is decreased, leading to increased susceptibility to infection. Granulocyte colony-stimulating factor (GCSF) has been the ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.107403
更新日期：2019-12-01 00:00:00
abstract：:The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capab...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)00038-7
更新日期：1997-08-01 00:00:00
abstract：:Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us under...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.06.010
更新日期：2017-12-01 00:00:00
abstract：:Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.pharmthera.2009.05.006
更新日期：2009-09-01 00:00:00
abstract：:High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many D...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.12.005
更新日期：2019-04-01 00:00:00
abstract：:Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, pneumonia, mechanical ventilation, and respiratory failure in infants in the US. No effective post-infection treatments are widely available, and currently there is no vaccine. RSV disease is the result of virus-induced airway damage and complex ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.04.008
更新日期：2006-11-01 00:00:00
abstract：:Injury to peripheral or spinal nerves following either trauma or disease has several consequences including the development of neuropathic pain. This syndrome is often refractory against conventional analgesics; and thus, novel medicaments are desired for its treatment. Recent studies have emphasized that dysfunction ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
doi：10.1016/j.pharmthera.2009.03.018
更新日期：2009-07-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90015-r
更新日期：1992-01-01 00:00:00
abstract：:Three major types of opioid receptors, designated mu, delta, and kappa, are widely expressed in the CNS. Development of selective receptor ligands and recent cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. It is of interest...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(00)00099-1
更新日期：2001-01-01 00:00:00
abstract：:The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107628
更新日期：2020-11-01 00:00:00
abstract：:In the heart, Ca(2+) released from the intracellular Ca(2+) storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca(2+) release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, inclu...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.06.002
更新日期：2008-09-01 00:00:00
