Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
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TLDR
The ways in which S1P might be therapeutically targeted are discussed — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S 1P and via thedevelopment of specific S1p receptor agonists.Abstract:
The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted — for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.read more
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Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction
Yashu Kuang,Xiaolin Li,Xiuxiang Liu,Lu Wei,Xiaoli Chen,Jie Liu,Tao Zhuang,Jingjiang Pi,Yanfang Wang,Chenying Zhu,Xin Gong,Hao Hu,Zuoren Yu,Jiming Li,Ping Yu,Huimin Fan,Yuzhen Zhang,Zhongmin Liu,Lin Zhang +18 more
TL;DR: It is revealed that cardiac microvascular endothelium promotes reparative macrophage proliferation in injured hearts via the S1P/S1PR1/ERK/CSF1 pathway and thus ameliorates post-MI adverse cardiac remodeling.
Journal ArticleDOI
Sphingosine-1-Phosphate Mediates a Reciprocal Signaling Pathway between Stellate Cells and Cancer Cells that Promotes Pancreatic Cancer Growth
Yan Bi,Jiachu Li,Jiachu Li,Baoan Ji,Ningling Kang,Liu Yang,Douglas A. Simonetto,Jung H. Kwon,Marielle J. Kamath,Sheng Cao,Vijay H. Shah +10 more
TL;DR: Pancreatic cancer cell-derived sphingosine-1-phosphate activates PSCs to release paracrine factors, including matrix metalloproteinase-9, which reciprocally promotes tumor cell migration and invasion in vitro and cancer growth in vivo.
Journal ArticleDOI
Sphingosine kinase 1 overexpression is associated with poor prognosis and oxaliplatin resistance in hepatocellular carcinoma.
Fangping Wang,Zhiming Wu +1 more
TL;DR: The present study is the first to report that SphK1 is associated with poor prognosis and oxaliplatin resistance in HCC and the findings have provided a direction for the identification of novel therapeutic targets for the treatment of HCC.
Journal ArticleDOI
Exploring the role of sphingolipid machinery during the epithelial to mesenchymal transition program using an integrative approach
Anastasia Meshcheryakova,Martin Svoboda,Ammar Tahir,Harald Köfeler,Alexander Triebl,Felicitas Mungenast,Georg Heinze,Christopher Gerner,Philip Zimmermann,Markus Jaritz,Diana Mechtcheriakova +10 more
TL;DR: The sphingolipid/EMT signature was identified primarily in lung adenocarcinoma tissues; besides, bladder, colorectal and prostate cancers were among the top-ranked tissues and the findings also highlight novel regulatory associations between influenza virus and the sphingosine 1-phosphate-/ceramide-metabolizing enzymes and S1P transporters.
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Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks
Laura Riboni,Loubna Abdel Hadi,Stefania Elena Navone,Laura Guarnaccia,Laura Guarnaccia,Rolando Campanella,Giovanni Marfia +6 more
TL;DR: How sphingosine-1-phosphate signaling contributes to favor cancer hallmarks including enhancement of proliferation, stemness, invasion, death resistance, angiogenesis, immune evasion and, possibly, aberrant metabolism is described.
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