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S1P Cancer

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https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#1
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28587987/sphingosine-kinase-1-sk1-allosteric-inhibitors-that-target-the-dimerization-site
#2
Ozge Bayraktar, Elif Ozkirimli, Kutlu Ulgen
The sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) signaling pathway is a crucial target for numerous human diseases from cancer to cardiovascular diseases. However, available SK1 inhibitors that target the active site suffer from poor potency, selectivity and pharmacokinetic properties. The selectivity issue of the kinases, which share a highly-conserved ATP-pocket, can be overcome by targeting the less-conserved allosteric sites. SK1 is known to function minimally as a dimer; however, the crystal structure of the SK1 dimer has not been determined...
May 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28570482/targeting-the-s1p-s1pr1-axis-mitigates-cancer-induced-bone-pain-and-neuroinflammation
#3
Shaness A Grenald, Timothy M Doyle, Hong Zhang, Lauren M Slosky, Zhoumou Chen, Tally M Largent-Milnes, Sarah Spiegel, Todd W Vanderah, Daniela Salvemini
Metastatic bone pain is the single most common form of cancer pain, and persists as a result of peripheral and central inflammatory, as well as, neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P)...
May 31, 2017: Pain
https://www.readbyqxmd.com/read/28560513/immunohistochemical-detection-of-sphingosine-1-phosphate-and-sphingosine-kinase-1-in-human-tissue-samples-and-cell-lines
#4
Gary M Reynolds, Barbara Visentin, Roger Sabbadini
Sphingosine-1-phosphate (S1P) and the enzyme primarily responsible for its production, sphingosine kinase-1 (SphK-1), are dysregulated in multiple human diseases including cancer, multiple sclerosis (MS), diabetes, neurological diseases, fibrosis, and certain pathologies associated with impaired angiogenesis such as age-related macular degeneration (AMD). Antibody-based techniques to identify and localize S1P and SphK-1 within cells and tissue specimens represent a powerful tool, not only to understand biological role of these molecules but also to validate these unique in-class targets in multiple state diseases...
May 31, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#5
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28482915/dr5-suppression-induces-sphingosine-1-phosphate-dependent-traf2-polyubiquitination-leading-to-activation-of-jnk-ap-1-and-promotion-of-cancer-cell-invasion
#6
You-Take Oh, Ping Yue, Shi-Yong Sun
BACKGROUND: Death receptor (DR5), a well-characterized death domain-containing cell surface pro-apoptotic protein, has been suggested to suppress cancer cell invasion and metastasis. However, the underlying mechanisms have not been fully elucidated. Our recent work demonstrates that DR5 suppression promotes cancer cell invasion and metastasis through caspase-8/TRAF2-mediated activation of ERK and JNK signaling and MMP1 elevation. The current study aimed at addressing the mechanism through which TRAF2 is activated in a caspase-8 dependent manner...
May 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28460443/sphingosine-1-phosphate-promotes-ovarian-cancer-cell-proliferation-by-disrupting-hippo-signaling
#7
Qianlan Fan, Yuan Cheng, Hsun-Ming Chang, Masashi Deguchi, Aaron J Hsueh, Peter C K Leung
Epithelial ovarian carcinomas account for more than 90% of human ovarian cancers and have become the primary cause of death for gynecological malignancies. Unlimited cell proliferation and resistance to cell apoptosis contribute to the development of ovarian cancers. However, the underlying mechanisms involved in these processes in epithelial ovarian carcinomas are yet poorly understood. In the present study, we examined the Hippo signaling gene expression and investigated the effects of Sphingosine 1-phosphate (S1P) on cell proliferation and the underlying mechanisms in human ovarian cancer cell lines, OVCAR3 and SKOV3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454397/sphingosine-kinase-1-a-novel-independent-prognosis-biomarker-in-hepatocellular-carcinoma
#8
Huajie Cai, Xuemeng Xie, Ling Ji, Xiaojiao Ruan, Zhihai Zheng
Sphingosine kinase 1 (Sphk1) is an oncogenic kinase that is responsible for the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). Mounting evidence suggests that Sphk1 serves a crucial role in the proliferation and development of a variety of human cancer cells. However, the role of Sphk1 in hepatocellular carcinoma (HCC) has not been fully elucidated. Therefore, the expression of Sphk1 was examined in 127 formalin-fixed, paraffin-embedded HCC tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28415564/mammalian-sphingosine-kinase-sphk-isoenzymes-and-isoform-expression-challenges-for-sphk-as-an-oncotarget
#9
REVIEW
Diana Hatoum, Nahal Haddadi, Yiguang Lin, Najah T Nassif, Eileen M McGowan
The various sphingosine kinase (SphK) isoenzymes (isozymes) and isoforms, key players in normal cellular physiology, are strongly implicated in cancer and other diseases. Mutations in SphKs, that may justify abnormal physiological function, have not been recorded. Nonetheless, there is a large and growing body of evidence demonstrating the contribution of gain or loss of function and the imbalance in the SphK/S1P rheostat to a plethora of pathological conditions including cancer, diabetes and inflammatory diseases...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406646/transforming-sphingosine-kinase-1-inhibitors-into-dual-and-sphingosine-kinase-2-selective-inhibitors-design-synthesis-and-in-vivo-activity
#10
Elizabeth S Childress, Yugesh Kharel, Anne M Brown, David R Bevan, Kevin R Lynch, Webster L Santos
Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P1-5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this article, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK...
May 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28377281/novel-sphingosine-kinase-1-inhibitor-lcl351-reduces-immune-responses-in-murine-dss-induced-colitis
#11
Michael J Pulkoski-Gross, Joachim D Uys, K Alexa Orr-Gandy, Nicolas Coant, Agnieszka B Bialkowska, Zdzislaw M Szulc, Aiping Bai, Alicja Bielawska, Danyelle M Townsend, Yusuf A Hannun, Lina M Obeid, Ashley J Snider
Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite which has been implicated in many diseases including cancer and inflammatory diseases. Recently, sphingosine kinase 1 (SK1), one of the isozymes which generates S1P, has been implicated in the development and progression of inflammatory bowel disease (IBD). Based on our previous work, we set out to determine the efficacy of a novel SK1 selective inhibitor, LCL351, in a murine model of IBD. LCL351 selectively inhibits SK1 both in vitro and in cells...
May 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28364399/sphingosine-1-phosphate-sphingosine-kinase-1-dependent-lymph-node-metastasis-in-esophageal-squamous-cell-carcinoma
#12
Yuta Kawakita, Satoru Motoyama, Yusuke Sato, Souichi Koyota, Akiyuki Wakita, Jiajia Liu, Hajime Saito, Yoshihiro Minamiya
PURPOSE: To establish whether Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SphK1) contribute to lymph node metastasis in esophageal squamous cell carcinoma. METHODS: Immunohistochemical analysis of SphK1 expression was performed using a tissue microarray containing 177 thoracic squamous cell esophageal cancer specimens resected at surgery, to investigate the association between intratumoral SphK1 expression and lymph node metastasis. Serum S1P levels and intratumoral SphK1 mRNA and protein expression were also evaluated in mice with vs...
March 31, 2017: Surgery Today
https://www.readbyqxmd.com/read/28362332/sphingosine-1-phosphate-metabolism-and-its-role-in-the-development-of-inflammatory-bowel-disease
#13
REVIEW
Tomasz Wollny, Marzena Wątek, Bonita Durnaś, Katarzyna Niemirowicz, Ewelina Piktel, Małgorzata Żendzian-Piotrowska, Stanisław Góźdź, Robert Bucki
Beyond their role as structural molecules, sphingolipids are involved in many important cellular processes including cell proliferation, apoptosis, inflammation, and migration. Altered sphingolipid metabolism is observed in many pathological conditions including gastrointestinal diseases. Inflammatory bowel disease (IBD) represents a state of complex, unpredictable, and destructive inflammation of unknown origin within the gastrointestinal tract. The mechanisms explaining the pathophysiology of IBD involve signal transduction pathways regulating gastro-intestinal system's immunity...
March 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28351953/sphingosine-1-phosphate-signaling-through-its-receptor-s1p5-promotes-chromosome-segregation-and-mitotic-progression
#14
Guillaume Andrieu, Adeline Ledoux, Sophie Branka, Magalie Bocquet, Julia Gilhodes, Thierry Walzer, Kousuke Kasahara, Masaki Inagaki, Roger A Sabbadini, Olivier Cuvillier, Anastassia Hatzoglou
Sphingosine kinase 1 (SphK1) promotes cell proliferation and survival, and its abundance is often increased in tumors. SphK1 produces the signaling lipid sphingosine 1-phosphate (S1P), which activates signaling cascades downstream five G protein-coupled receptors (S1P1-5) to modulate vascular and immune system function and promote proliferation. We identified a new function of the SphK1-S1P pathway specifically in the control of mitosis. SphK1 depletion in HeLa cells caused prometaphase arrest, whereas its overexpression or activation accelerated mitosis...
March 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/28322796/modulation-of-the-sphingolipid-rheostat-is-involved-in-paclitaxel-resistance-of-the-human-prostate-cancer-cell-line-pc3-pr
#15
Yuka Aoyama, Sayaka Sobue, Naoki Mizutani, Chisato Inoue, Yoshiyuki Kawamoto, Yuji Nishizawa, Masatoshi Ichihara, Mamoru Kyogashima, Motoshi Suzuki, Yoshinoti Nozawa, Takashi Murate
Taxoids are anti-cancer drugs frequently used to treat solid tumors, but they are sometimes ineffective and tumors may become resistant to their action. Here, we examined the involvement of sphingolipid metabolic enzymes in paclitaxel (PTX) resistance using a human prostate cancer cell line, PC3, and its PTX-resistant subline, PC3-PR. PTX (20 nM) suppressed cell proliferation and increased various ceramide species in PC3, but not PC3-PR, cells. PC3-PR contained higher S1P levels than did PC3, regardless of PTX treatment...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302566/mechanisms-of-sphingosine-1-phosphate-receptor-signalling-in-cancer
#16
REVIEW
Sathya Narayanan Patmanathan, Wei Wang, Lee Fah Yap, Deron R Herr, Ian C Paterson
S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1-5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28279838/modulation-of-sphingosine-1-phosphate-in-inflammatory-bowel-disease
#17
REVIEW
Laurent Peyrin-Biroulet, Ronald Christopher, Dominic Behan, Cheryl Lassen
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, involve an inappropriate immune reaction in the digestive tract, causing a variety of disabling symptoms. The advent of monoclonal antibodies (anti-tumor necrosis factor, anti-integrin, anti-interleukin -23) has revolutionized IBD management. Nevertheless, these agents, with potential for immunogenicity, are associated with high rates of response loss and disease relapse over time. They are also associated with high production costs...
March 7, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28270699/fty720-attenuates-angiotensin-ii-induced-podocyte-damage-via-inhibiting-inflammatory-cytokines
#18
Ke Su, Ping Zeng, Wei Liang, Zhengyu Luo, Yiman Wang, Xifeng Lv, Qi Han, Miao Yan, Cheng Chen
FTY720, a new chemical substance derived from the ascomycete Isaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28270071/inhibitory-effects-of-novel-sphk2-inhibitors-on-migration-of-cancer-cells
#19
Deokho Jung, Junghyun Jung, Euiyeon Lee, Chang Soo Mok, Hyunjin Jeon, Chang Seo Park, Wonhee Jang, Youngeun Kwon
Cell migration is an essential process for survival and differentiation of mammalian cells. Numerous diseases are induced or influenced by inappropriate regulation of cell migration, which plays a key role in cancer cell metastasis. In fact, very few anti-metastasis drugs are available on the market. SphKs are enzymes that convert sphingosine to sphingosine-1- phosphate (S1P) and are known to control various cellular functions, including migration of cells. Among two human isozymes of SphK2, SphK2 is known to promote apoptosis, suppresses cell growth, and controls cell migration; in addition, the specific ablation of SphK2 activity was reported to inhibit cancer cell metastasis...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28248965/pancreas-lineage-allocation-and-specification-are-regulated-by-sphingosine-1-phosphate-signalling
#20
Ioannis Serafimidis, Eva Rodriguez-Aznar, Mathias Lesche, Kazuaki Yoshioka, Yoh Takuwa, Andreas Dahl, Duojia Pan, Anthony Gavalas
During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated...
March 2017: PLoS Biology
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