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
Lipid metabolic reprogramming in cancer cells
TL;DR: In it, detailed insight is provided into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells.
Journal ArticleDOI
Natural product and natural product derived drugs in clinical trials
TL;DR: The next few years will be critical for NP-driven lead discovery, and a concerted effort is required to identify new biologically active pharmacophores and to progress these and existing compounds through pre-clinical drug development into clinical trials.
Journal ArticleDOI
The Concise Guide to PHARMACOLOGY 2013/14: Enzymes
Stephen P.H. Alexander,Helen E. Benson,Elena Faccenda,Adam J. Pawson,Joanna L. Sharman,Michael Spedding,John A. Peters,Anthony J. Harmar +7 more
TL;DR: The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
Journal ArticleDOI
An update on the biology of sphingosine 1-phosphate receptors.
Victoria A. Blaho,Timothy Hla +1 more
TL;DR: This review will focus on the most recent advances in S1PRs, as they become attractive therapeutic targets in several diseases, such as chronic inflammatory pathologies, autoimmunity, and cancer.
Journal ArticleDOI
STAT3 Target Genes Relevant to Human Cancers
Richard L. Carpenter,Hui-Wen Lo +1 more
TL;DR: A review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.
References
More filters
Journal ArticleDOI
S1P1-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fate.
Euijung Jo,M. Germana Sanna,Pedro J. Gonzalez-Cabrera,Shobha Thangada,Gabor Tigyi,Daniel A. Osborne,Timothy Hla,Abby L. Parrill,Hugh Rosen +8 more
TL;DR: SEW2871 recapitulates the action of S1P in all the signaling pathways examined and overlaps in interactions with key headgroup binding receptor residues, presumably replacing salt-bridge interactions with ion-dipole interactions.
Journal ArticleDOI
Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1.
Mark E. Schnute,Matthew D. McReynolds,Tom Kasten,Matthew P. Yates,Gina M. Jerome,John W. Rains,Troii Hall,Jill Chrencik,Michelle Kraus,Ciarán N. Cronin,Matthew J. Saabye,Maureen K. Highkin,Richard M. Broadus,Shinji Ogawa,Kristin Cukyne,Laura E. Zawadzke,Vincent Peterkin,Kaliapan Iyanar,Jeffrey A. Scholten,Jay M. Wendling,Hideji Fujiwara,Olga V. Nemirovskiy,Arthur J. Wittwer,Marek M. Nagiec +23 more
TL;DR: PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of Sphk1-driven S1P signalling, indicating that the SphK 1 isoform of sphingosine kinase is the major source of S 1P in human blood.
Journal ArticleDOI
Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis.
Sahar A. Saddoughi,Salih Gencer,Yuri K. Peterson,Katherine E. Ward,Archana Mukhopadhyay,Joshua J. Oaks,Jacek Bielawski,Zdzislaw M. Szulc,Raquela J. Thomas,Shanmugam Panneer Selvam,Can E. Senkal,Elizabeth Garrett-Mayer,Ryan M. De Palma,Dzmitry Fedarovich,Angen Liu,Amyn A. Habib,Amyn A. Habib,Robert V. Stahelin,Robert V. Stahelin,Danilo Perrotti,Besim Ogretmen +20 more
TL;DR: Data suggest that targeting I2PP2A/SET by FTY720 suppresses lung tumour growth, at least in part, via PP2A activation and necroptosis mediated by the kinase domain of RIPK1.
Journal ArticleDOI
S1PR1-STAT3 Signaling Is Crucial for Myeloid Cell Colonization at Future Metastatic Sites
Jiehui Deng,Yong Liu,Heehyoung Lee,Andreas Herrmann,Wang Zhang,Chunyan Zhang,Shudan Shen,Saul J. Priceman,Maciej Kujawski,Sumanta K. Pal,Andrew Raubitschek,Dave S.B. Hoon,Stephen J. Forman,Robert A. Figlin,Jie Liu,Richard Jove,Hua Yu +16 more
TL;DR: It is shown that S1PR1-STAT3 upregulation in tumor cells induces factors that activate S1 PR1- STAT3 in various cells in premetastatic sites, leading to premetASTatic niche formation.
Journal ArticleDOI
Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: the role of sphingosine kinase-1
Olga A. Sukocheva,Carol Wadham,Andrew B. Holmes,Nathaniel Albanese,Emily Verrier,Feng Feng,Alex Bernal,Claudia K. Derian,Axel Ullrich,Mathew A. Vadas,Pu Xia +10 more
TL;DR: It is demonstrated that E2-induced EGFR transactivation in human breast cancer cells is driven via a novel signaling system controlled by the lipid kinase sphingosine kinase-1 (SphK1), which reveals a key role for SphK1 in the coupling of the signals between three membrane-spanning events induced by E2, S1P, and EGF.