Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
2-Aminobenzoxazole Derivatives as Potent Inhibitors of the Sphingosine-1-Phosphate Transporter Spinster Homolog 2 (Spns2).
Ariel L Burgio,Chris Shrader,Yugesh Kharel,Tao Huang,Joseph M. Salamoun,Kevin R. Lynch,Webster L. Santos +6 more
TL;DR: In this article , the S1P1 receptor is the target of four marketed drugs for the treatment of multiple sclerosis and ulcerative colitis without cardiac toxicity, and the first Spns2 inhibitor SLF1081851 (16d) was reported.
Dissertation
On the role of bioactive sphingolipids and their metabolizing enzymes in cancer
TL;DR: It is concluded that targeting these enzymes could potentiate other treatment effects in HCC and bladder cancer cells, and that inhibition of sphingosine kinase 1 enhances cytotoxicity, ceramide levels and ROS formation in liver cancer cells treated with selenite.
Journal ArticleDOI
Induction of hemangiosarcoma in mice after chronic treatment with S1P-modulator siponimod and its lack of relevance to rat and human
Francois Pognan,J. Andreas Mahl,Maria Papoutsi,David Ledieu,Marc Raccuglia,Diethilde Theil,Sarah B. Voytek,Patrick J. Devine,Katie Kubek-Luck,Natalie M. Claudio,André Cordier,Annabelle Heier,Carine Kolly,Andreas Hartmann,Salah-Dine Chibout,Page Bouchard,Christian Trendelenburg +16 more
TL;DR: The molecular mechanisms leading to siponimod-induced HSA in mice are considered species specific and likely irrelevant to humans, while it is suggested that the human cells also reproduce a lack of in vivo response to sip onimod.
Journal ArticleDOI
Sphingosine kinases regulate ER contacts with late endocytic organelles and cholesterol trafficking
Elisa N.D. Palladino,Tytus Bernas,Chris D. Green,Cynthia Weigel,Sandeep Singh,Can E. Senkal,Andrea Martello,John P. Kennelly,Erhard Bieberich,Peter Tontonoz,David A. Ford,Sheldon Milstien,Emily R. Eden,Sarah Spiegel +13 more
TL;DR: A previously unknown role for SphKs and sphingolipid metabolites in governing diverse MCS between the ER network and late endocytic organelles versus the PM to control the movement of cholesterol between distinct cell membranes is revealed.
Dissertation
Metabolic dysfunction and impairments in the DNA Damage Response: dissecting a pathomechanistic link betweenMicrocephalic Primordial Dwarfisms and cancer cachexia
TL;DR: Characterised novel effects of ATR deficiency in adipocyte differentiation and metabolism, and ER and autophagic functionality and discovered ATR at the ER membrane, where ATRi-induced vacuolisation was derived from swollen endoplasmic reticulum (ER) concomitant with ER stress.
References
More filters
Journal ArticleDOI
STATs in cancer inflammation and immunity: a leading role for STAT3
TL;DR: Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Journal ArticleDOI
Principles of bioactive lipid signalling: lessons from sphingolipids
TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
Journal ArticleDOI
The many roles of histone deacetylases in development and physiology: Implications for disease and therapy
TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Journal Article
Heart-lung transplantation.
TL;DR: A broad overview of the various grounds upon which this difference is likely based and discuss recent advances in each area: 1) criteria for the selection of candidates and donors, 2) methods for ex-vivo preservation of donor organs, 3) technical execution of the operative procedure, and 4) prevention of postoperative infection as discussed by the authors.
Journal ArticleDOI
Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase
Liming Sun,Huayi Wang,Zhigao Wang,Sudan He,She Chen,Daohong Liao,Lai Wang,Jiacong Yan,Weilong Liu,Xiaoguang Lei,Xiaodong Wang +10 more
TL;DR: The identification of a small molecule called necrosulfonamide that specifically blocks necrosis downstream of RIP3 activation is reported, which implicate MLKL as a key mediator of necrosis signaling downstream of the kinase RIP3.