Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg? Journal Article

Authors: Lee, W. K.; Kolesnick, R. N.
Article Title: Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?
Abstract: The cancer multidrug resistance (MDR) phenotype encompasses a myriad of molecular, genetic and cellular alterations resulting from progressive oncogenic transformation and selection. Drug efflux transporters, in particular the MDR P-glycoprotein ABCB1, play an important role in MDR but cannot confer the complete phenotype alone indicating parallel alterations are prerequisite. Sphingolipids are essential constituents of lipid raft domains and directly participate in functionalization of transmembrane proteins, including providing an optimal lipid microenvironment for multidrug transporters, and are also perturbed in cancer. Here we postulate that increased sphingomyelin content, developing early in some cancers, recruits and functionalizes plasma membrane ABCB1 conferring a state of partial MDR, which is completed by glycosphingolipid disturbance and the appearance of intracellular vesicular ABCB1. In this review, the independent and interdependent roles of sphingolipid alterations and ABCB1 upregulation during the transformation process and resultant conferment of partial and complete MDR phenotypes are discussed. © 2017 Elsevier Inc.
Keywords: chemotherapy; drug resistance; sphingomyelin; glucosylceramide; lipid rafts; neoplastic progression
Journal Title: Cellular Signalling
Volume: 38
ISSN: 0898-6568
Publisher: Elsevier Inc.  
Date Published: 2017-10-01
Start Page: 134
End Page: 145
Language: English
DOI: 10.1016/j.cellsig.2017.06.017
PROVIDER: scopus
PUBMED: 28687494
PMCID: PMC5726251
Notes: Review -- Export Date: 2 August 2017 -- Source: Scopus
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MSK Authors
  1. Richard N Kolesnick
    230 Kolesnick
  2. Wing-Kee Lee
    2 Lee