New insights into the roles and regulation of SphK2 as a therapeutic target in cancer chemoresistance

Development of multidrug resistance (MDR) is still a big obstacle against successful and complete cancer treatment. Sphingosine kinase 2 targeting could provide a novel approach and a potentially more effective treatment strategy for MDR in cancer. AbstractChemoresistance is a complicated process developed by most cancers and accounts for the majority of relapse and metastasis in cancer. The main mechanisms of chemoresistance phenotype include increased expression and/or activated drug efflux pumps, altered DNA repair, altered metabolism of therapeutics as well as impaired apoptotic signaling pathways. Aberrant sphingolipid signaling has also recently received considerable attention in chemoresistance. Sphingolipid metabolites regulate main biological processes such as apoptosis, cell survival, proliferation, and differentiation. Two sphingosine kinases, SphK1 and SphK2, convert sphingosine to sphingosine ‐1‐phosphate, an antiapoptotic bioactive lipid mediator. Numerous evidence has revealed the involvement of activated SphK1 in tumorigenesis and resistance, however, contradictory results have been found for the role of SphK2 in these functions. In some studies, overexpression of SphK2 suppressed cell growth and induced apoptosis. In contrast, some others have shown cell proliferation and tumor promotion effect for SphK2. Our understanding of the role of SphK2 in cancer does not have a sufficient integrity. The main focus of this review will be on the re‐evaluation of t...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: REVIEW ARTICLE Source Type: research