title: Mechanisms of sphingosine 1-phosphate receptor signalling in cancer.
abstract: 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. However, cooperativity between the individual S1PRs, functional interactions with receptor tyrosine kinases and the sub-cellular localisation of the S1PRs within tumour cells also appear to play a role in mediating the effects of S1PR signalling during carcinogenesis. Here we review what is known regarding the role of individual S1PRs in cancer and discuss the recent evidence to suggest cross-talk between the S1PRs and other cellular signalling pathways in cancer. We will also discuss the therapeutic potential of targeting the S1PRs and their downstream signalling pathways for the treatment of cancer.
authors.affiliation: Department of Oral and Craniofacial Sciences, Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sathya Narayanan
authors.initials: SN
authors.lastname: Patmanathan
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oral and Craniofacial Sciences, Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Lee Fah
authors.initials: LF
authors.lastname: Yap
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore.
authors.forename: Deron R
authors.initials: DR
authors.lastname: Herr
authors.affiliation: Department of Oral and Craniofacial Sciences, Oral Cancer Research & Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: ipaterson@um.edu.my.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Paterson
mesh_terms: D000818:Animals; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D020794:Receptor Protein-Tyrosine Kinases; D013110:Sphingosine
keywords: Cancer; GPCR; Sphingosine 1-phosphate