Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies

Evangelisti, C and Evangelisti, C and Buontempo, F and Lonetti, A and Orsini, E and Chiarini, F and Barata, J T and Pyne, S and Pyne, N J and Martelli, A M (2016) Therapeutic potential of targeting sphingosine kinases and sphingosine 1-phosphate in hematological malignancies. Leukemia, 30. 2142–2151. ISSN 0887-6924

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    Abstract

    Sphingolipids, such as ceramide, sphingosine and sphingosine 1-phosphate (S1P) are bioactive molecules that have important functions in a variety of cellular processes, which include proliferation, survival, differentiation and cellular responses to stress. Sphingolipids have a major impact on the determination of cell fate by contributing to either cell survival or death. Although ceramide and sphingosine are usually considered to induce cell death, S1P promotes survival of cells. Sphingosine kinases (SPHKs) are the enzymes that catalyze the conversion of sphingosine to S1P. There are two isoforms, SPHK1 and SPHK2, which are encoded by different genes. SPHK1 has recently been implicated in contributing to cell transformation, tumor angiogenesis and metastatic spread, as well as cancer cell multidrug-resistance. More recent findings suggest that SPHK2 also has a role in cancer progression. This review is an overview of our understanding of the role of SPHKs and S1P in hematopoietic malignancies and provides information on the current status of SPHK inhibitors with respect to their therapeutic potential in the treatment of haematological cancers.

    Author(s):Evangelisti, C, Evangelisti, C, Buontempo, F, Lonetti, A, Orsini, E, Chiarini, F, Barata, J T, Pyne, S ORCID logoORCID: https://orcid.org/0000-0002-6608-9584, Pyne, N J ORCID logoORCID: https://orcid.org/0000-0002-5657-4578 and Martelli, A M
    Item type:Article
    ID code:57738
    Keywords:apoptosis, ceramide, drug-resistance, leukemia, lymphoma, multiple myeloma, sphingosine, sphingosine 1-phosphate, Neoplasms. Tumors. Oncology (including Cancer), Therapeutics. Pharmacology, Oncology, Pharmacology, Toxicology and Pharmaceutics(all)
    Subjects:Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
    Medicine > Therapeutics. Pharmacology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:09 Sep 2016 08:49
    Last modified:15 Jan 2020 21:02
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/57738
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