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S1P Cancer

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https://www.readbyqxmd.com/read/29790626/sphingosine-1-phosphate-promotes-the-proliferation-and-attenuates-apoptosis-of-endothelial-progenitor-cells-via-s1pr1-s1pr3-pi3k-akt-pathway
#1
Hang Wang, Hao Huang, Shi-Fang Ding
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist ), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs...
May 23, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#2
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29750961/apolipoprotein-m-promotes-proliferation-and-invasion-in-non-small-cell-lung-cancers-via-upregulating-s1pr1-and-activating-the-erk1-2-and-pi3k-akt-signaling-pathways
#3
Yifei Zhu, Guanghua Luo, Bo Jiang, Miaomei Yu, Yuehua Feng, Min Wang, Ning Xu, Xiaoying Zhang
Apolipoprotein M (ApoM) is a sphingosine 1-phosphate (S1P) carrier involved in the regulation of S1P. Signaling pathways involving sphingosine kinases (SphKs) and S1P-S1P receptors (S1PRs) play important roles in the oncogenesis of multiple cancers including non-small cell lung cancer (NSCLC). In the present study we have clarified the potential roles of ApoM on the oncogenesis process of NSCLC cells. We detected the ApoM expression in NSCLC tissues and further analyzed its clinical significance. Moreover, we determined effects of ApoM overexpression on tumor cellular behaviours of NSCLC in vitro and in vivo...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29748384/balance-between-senescence-and-apoptosis-is-regulated-by-telomere-damage-induced-association-between-p16-and-caspase-3
#4
Shanmugam Panneer Selvam, Braden M Roth, Rose Nganga, Jisun Kim, Marion A Cooley, Kristi L Helke, Charles D Smith, Besim Ogretmen
Telomerase activation protects cells from telomere damage by delaying senescence and inducing cell immortalization, whereas telomerase inhibition mediates rapid senescence or apoptosis. However, the cellular mechanisms that determine telomere damage-dependent senescence versus apoptosis induction are largely unknown. Here, we demonstrate that telomerase instability mediated by silencing of sphingosine kinase 2 (SPHK2) and sphingosine 1-phosphate (S1P), which binds and stabilizes telomerase, induces telomere damage-dependent caspase-3 activation and apoptosis, but not senescence, in p16-deficient lung cancer cells or tumors...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29734379/sphingosine-1-phosphate-attenuates-mmp2-and-mmp9-in-human-anaplastic-thyroid-cancer-c643-cells-importance-of-s1p2
#5
Muhammad Yasir Asghar, Kati Kemppainen, Taru Lassila, Kid Törnquist
In anaplastic thyroid cancer C643 cells, sphingosine 1-phosphate (S1P) attenuates migration by activating the S1P2 receptor and the Rho-ROCK pathway. In the present study, we show that stimulating C643 cells with S1P decreases the expression, secretion and activity of matrix metalloproteinase-2 (MMP2), and to a lesser extent MMP9. Using receptor-specific antagonists, and S1P2 siRNA, we showed that the inhibition of expression of MMP2 is mediated through S1P2. Furthermore, S1P inhibited calpain activity, and inhibiting calpain pharmacologically, inhibited the effect of S1P on MMP2 expression and activity, and on MMP9 activity...
2018: PloS One
https://www.readbyqxmd.com/read/29718989/first-evidence-of-sgpl1-expression-in-the-cell-membrane-silencing-the-extracellular-s1p-siren-in-mammary-epithelial-cells
#6
Nadja Engel, Anna Adamus, Marcus Frank, Karin Kraft, Juliane Kühn, Petra Müller, Barbara Nebe, Annika Kasten, Guido Seitz
The bioactive lipid sphingosine-1-phosphate (S1P) is a main regulator of cell survival, proliferation, motility, and platelet aggregation, and it is essential for angiogenesis and lymphocyte trafficking. In that S1P acts as a second messenger intra- and extracellularly, it might promote cancer progression. The main cause is found in the high S1P concentration in the blood, which encourage cancer cells to migrate through the endothelial barrier into the blood vessels. The irreversible degradation of S1P is solely caused by the sphingosine-1-phosphate lyase (SGPL1)...
2018: PloS One
https://www.readbyqxmd.com/read/29662189/akt-as-a-key-target-for-growth-promoting-functions-of-neutral-ceramidase-in-colon-cancer-cells
#7
Nicolas Coant, Mónica García-Barros, Qifeng Zhang, Lina M Obeid, Yusuf A Hannun
Despite advances in the field, colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Research into bioactive sphingolipids over the past two decades has played an important role in increasing our understanding of the pathogenesis and therapeutics of CRC. In the complex metabolic network of sphingolipids, ceramidases (CDases) have a key function. These enzymes hydrolyze ceramides into sphingosine (SPH) which in turn is phosphorylated by sphingosine kinases (SK) 1 and 2 to generate sphingosine-1 phosphate (S1P)...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29643998/deletion-of-sphingosine-kinase-1-inhibits-liver-tumorigenesis-in-diethylnitrosamine-treated-mice
#8
Jinbiao Chen, Yanfei Qi, Yang Zhao, Dominik Kaczorowski, Timothy A Couttas, Paul R Coleman, Anthony S Don, Patrick Bertolino, Jennifer R Gamble, Mathew A Vadas, Pu Xia, Geoffrey W McCaughan
Primary liver cancer is the 3rd leading cause of cancer deaths worldwide with very few effective treatments. Sphingosine kinase 1 (SphK1), a key regulator of sphingolipid metabolites, is over-expressed in human hepatocellular carcinoma (HCC) and our previous studies have shown that SphK1 is important in liver injury. We aimed to explore the role of SphK1 specifically in liver tumorigenesis using the SphK1 knockout ( SphK1 -/- ) mouse. SphK1 deletion significantly reduced the number and the size of DEN-induced liver cancers in mice...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29623068/nuclear-insulin-like-growth-factor-binding-protein-3-as-a-biomarker-in-triple-negative-breast-cancer-xenograft-tumors-effect-of-targeted-therapy-and-comparison-with-chemotherapy
#9
Sohel M Julovi, Janet L Martin, Robert C Baxter
Triple-negative breast cancer (TNBC) typically has a worse outcome than other breast cancer subtypes, in part owing to a lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway in basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), in which the epidermal growth factor receptor (EGFR) is transactivated by sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted by combination treatment with the S1P receptor modulator and SphK inhibitor, fingolimod, and the EGFR kinase inhibitor, gefitinib (F + G)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29605826/triple-negative-breast-cancer-depends-on-sphingosine-kinase-1-sphk1-sphingosine-1-phosphate-s1p-sphingosine-1-phosphate-receptor-3-s1pr3-notch-signaling-for-metastasis
#10
Shushu Wang, Yueyang Liang, Wenxiao Chang, Baoquan Hu, Yi Zhang
BACKGROUND Triple negative breast cancer (TNBC) has a more aggressive recurrence. Previous reports have demonstrated that sphingosine kinase 1 (SphK1) is a crucial regulator of breast cancer progression. However, the correlation of SphK1 with clinical prognosis has been poorly investigated. Thus, we aimed to elaborate the role of SphK1 in TNBC metastasis. MATERIAL AND METHODS We first determined the level of SphK1 in breast cancer tissue samples and breast cancer cells. Furthermore, the expression of HER2 and phosphor-SphK1 (pSphK1) in human breast cancer tissue samples was determined by immunohistochemical analysis...
April 1, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29523764/abcc1-exported-sphingosine-1-phosphate-produced-by-sphingosine-kinase-1-shortens-survival-of-mice-and-patients-with-breast-cancer
#11
Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Wei-Ching Huang, Santiago Lima, Nitai C Hait, Aparna Maiti, Kumiko Kida, Krista P Terracina, Hiroshi Miyazaki, Takashi Ishikawa, Itaru Endo, Michael R Waters, Qianya Qi, Li Yan, Sheldon Milstien, Sarah Spiegel, Kazuaki Takabe
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid mediator, has been implicated in regulation of many processes important for breast cancer progression. Previously, we observed that S1P is exported out of human breast cancer cells by ATP-binding cassette (ABC) transporter ABCC1, but not by ABCB1, both known multidrug resistance proteins that efflux chemotherapeutic agents. However, the pathologic consequences of these events to breast cancer progression and metastasis have not been elucidated. Here, it is demonstrated that high expression of ABCC1, but not ABCB1, is associated with poor prognosis in breast cancer patients...
March 9, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29484372/sphingosine-kinase-inhibitors-a-patent-review
#12
Mengda Cao, Chunmei Ji, Yanjun Zhou, Wen Huang, Weiwei Ni, Xunliang Tong, Ji-Fu Wei
Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). SphK/S1P pathway has been linked to the progression of cancer and various other diseases including allergic inflammatory disease, cardiovascular diseases, rejection after transplantation, the central nervous system, and virus infections. Therefore, SphKs represent potential new targets for developing novel therapeutics for these diseases. The history and development of SphK inhibitors are discussed, summarizing SphK inhibitors by their structures, and describing some applications of SphK inhibitors...
May 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29467963/new-extracellular-factors-in-glioblastoma-multiforme-development-neurotensin-growth-differentiation-factor-15-sphingosine-1-phosphate-and-cytomegalovirus-infection
#13
REVIEW
Jan Korbecki, Izabela Gutowska, Ireneusz Kojder, Dariusz Jeżewski, Marta Goschorska, Agnieszka Łukomska, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29458005/14-3-3%C3%AE-promotes-esophageal-squamous-cell-carcinoma-invasion-by-repressing-s1pr2-protein-expression-through-nf-%C3%AE%C2%BAb-signaling
#14
Song Tong, Sheng-Cai Chen, Kai-Ying Xu, Bin Fang, Si-Hua Wang, Jian-Jun Wang
14-3-3ζ is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects...
April 2, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29385066/expansion-of-sphingosine-kinase-and-sphingosine-1-phosphate-receptor-function-in-normal-and-cancer-cells-from-membrane-restructuring-to-mediation-of-estrogen-signaling-and-stem-cell-programming
#15
REVIEW
Olga A Sukocheva
Sphingolipids, sphingolipid metabolizing enzymes, and their receptors network are being recognized as part of the signaling mechanisms, which govern breast cancer cell growth, migration, and survival during chemotherapy treatment. Approximately 70% of breast cancers are estrogen receptor (ER) positive and, thus, rely on estrogen signaling. Estrogen activates an intracellular network composed of many cytoplasmic and nuclear mediators. Some estrogen effects can be mediated by sphingolipids. Estrogen activates sphingosine kinase 1 (SphK1) and amplifies the intracellular concentration of sphingosine-1-phosphate (S1P) in breast cancer cells during stimulation of proliferation and survival...
January 31, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29377310/nuclear-lipid-mediators-role-of-nuclear-sphingolipids-and-sphinosine-1-phosphate-signaling-in-epigenetic-regulation-of-inflammation-and-gene-expression
#16
Panfeng Fu, David L Ebenezer, Alison W Ha, Vidyani Suryadevara, Anantha Harijith, Viswanathan Natarajan
Phospholipids, sphingolipids, and cholesterol are integral components of eukaryotic cell organelles, including the nucleus. Recent evidence shows characteristic features of nuclear lipid composition and signaling, which are distinct from that of the cytoplasm and plasma membrane. While the nuclear phosphoinositol lipid signaling in cell cycle regulation and differentiation has been well described, there is a paucity on the role of nuclear sphingolipids and sphingolipid signaling in different physiological and pathophysiological human conditions...
January 27, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29368980/tp53-is-required-for-becn1-and-atg5-dependent-cell-death-induced-by-sphingosine-kinase-1-inhibition
#17
Santiago Lima, Kazuaki Takabe, Jason Newton, Kumar Saurabh, Megan M Young, Andreia Machado Leopoldino, Nitai C Hait, Jane L Roberts, Hong-Gang Wang, Paul Dent, Sheldon Milstien, Laurence Booth, Sarah Spiegel
The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arrest, apoptosis, and macroautophagy/autophagy. However, little is still known of the relationship between TP53 and SPHK1 activity in the regulation of these processes. To explore this link, we examined the effects of inhibiting SPHK1 in wild-type and TP53 null cancer cell lines...
January 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#18
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
April 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29234668/a-genome-wide-screen-for-fty720-sensitive-mutants-reveals-genes-required-for-ros-homeostasis
#19
Kanako Hagihara, Kanako Kinoshita, Kouki Ishida, Shihomi Hojo, Yoshinori Kameoka, Ryosuke Satoh, Teruaki Takasaki, Reiko Sugiura
Fingolimod hydrochloride (FTY720), a sphingosine-1-phosphate (S1P) analogue, is an approved immune modulator for the treatment of multiple sclerosis (MS). Notably, in addition to its well-known mode of action as an S1P modulator, accumulating evidence suggests that FTY720 induces apoptosis in various cancer cells via reactive oxygen species (ROS) generation. Although the involvement of multiple signaling molecules, such as JNK (Jun N-terminal kinase), Akt (alpha serine/threonine-protein kinase) and Sphk has been reported, the exact mechanisms how FTY720 induces cell growth inhibition and the functional relationship between FTY720 and these signaling pathways remain elusive...
November 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29229990/tumor-suppressor-p53-links-ceramide-metabolism-to-dna-damage-response-through-alkaline-ceramidase-2
#20
Ruijuan Xu, Monica Garcia-Barros, Sally Wen, Fang Li, Chih-Li Lin, Yusuf A Hannun, Lina M Obeid, Cungui Mao
p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53...
December 11, 2017: Cell Death and Differentiation
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