Multidrug resistance: a role for cholesterol efflux pathways?
Multidrug resistance (MDR) severely impairs the efficacy of cancer chemotherapy. Several protein transporters that mediate drug export have been identified, but additional adaptations appear to be necessary for full-fledged drug resistance. The cell surface density of caveolae and the expression of the caveolar coat protein caveolin are dramatically increased in MDR cancer cells. Acquisition of MDR might thus be accompanied by upregulation of caveolin-dependent cholesterol efflux pathways, raising the possibility that these same pathways are utilized for delivering drugs from intracellular compartments to the plasma membrane, where drugs can be extruded from the cells by drug efflux ATPases. The upregulation of caveolin mandates a phenotypic change of MDR cells in terms of their cholesterol homeostasis and is accompanied by loss of important features of the transformed phenotype of MDR cancer cells.
Liscovitch
M
M
Dept of Biological Regulation, Weizmann Institute of Science, 76100, Rehovot, Israel. moti.liscovitch@weizmann.ac.il
Lavie
Y
Y
D001402:B-Lymphocytes / Q000378:metabolism; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D002784:Cholesterol