Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences
Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences
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DOI：
10.1023/a:1026553626537
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发表时间：
2000-03-01
影响因子：
3
通讯作者：
Liscovitch, M
中科院分区：
文献类型：
--
作者：
Lavie, Y;Liscovitch, M
致癌过程涉及一系列复杂的遗传和生化变化，使转化的细胞能够增殖，迁移到次级部位，在某些情况下，还会获得使癌细胞对化疗产生抗药性的机制。这种最常见的现象被称为多药耐药(MDR)。它通常是由P-糖蛋白(P-gp)或其他质膜ATPase的过度表达介导的，这些ATPase输出化疗中使用的细胞毒药物，从而降低其疗效。然而，为了获得完整的多药耐药表型，可能需要额外的适应性改变。最近的研究表明，MDR的获得伴随着构成脂筏和腔膜的脂类和蛋白质的上调，特别是葡萄糖神经酰胺和小窝蛋白。这些变化可能与以下事实有关：在MDR细胞中，很大一部分细胞P-gp与富含小窝蛋白的膜结构域有关，它们可能参与药物的转运，并可能对药物诱导的细胞凋亡和MDR癌细胞的表型转化产生影响。
The carcinogenic process Involves a complex series of genetic and biochemical changes that enables transformed cells to proliferate, migrate to secondary sites and, in some cases, acquire mechanisms that make cancer cells resistant to chemotherapy. This phenomenon in its most common form is known as multidrug resistance (MDR). It is usually mediated by overexpression of P-glycoprotein (P-gp) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. However, additional adaptive changes are likely to be required in order to confer a full MDR phenotype. Recent studies have shown that acquisition of MDR is accompanied by upregulation of lipids and proteins that constitute lipid rafts and caveolar membranes, notably glucosylceramide and caveolin. These changes may be related to the fact that in MDR cells a significant fraction of cellular P-gp is associated with caveolin-rich membrane domains, they may be involved in drug transport and they could have an impact on drug-induced apoptosis and on the phenotypic transformation of MDR cancer cells.