The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer
The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer
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DOI：
10.1158/0008-5472.can-04-3478
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发表时间：
2005-08-01
期刊：
影响因子：
11.2
通讯作者：
Rodríguez-Rodríguez, L
中科院分区：
文献类型：
--
作者：
Miletti-González, KE;Chen, SL;Rodríguez-Rodríguez, L
癌细胞的侵袭和转移以及对抗癌疗法的抗性的发展是癌症发病率和死亡率的主要原因。二十多年来，癌症生物学中这两个重要但不明确相关的方面已被广泛研究。具体而言，P-糖蛋白和CD 44已被表征，并且已知是多药耐药（MDR）和转移的决定因素。尽管有这样的知识体系，但很少有报道将这两种表型联系起来，直到最近才有理由怀疑它们之间存在直接联系。在这份报告中，我们表明，一种新的物理和遗传之间的相互作用CD 44和P-糖蛋白是部分负责MDR和癌细胞的侵袭潜力之间的相关性。干扰其功能的P-糖蛋白特异性底物减少了CD 44和P-糖蛋白的体外侵袭、迁移和物理共定位。CD 44在敏感细胞中的表达促进了P-糖蛋白的表达和MDR表型。MDR 1的RNA干扰抑制了细胞的迁移速率。这些数据表明，CD 44和P-糖蛋白之间存在密切的相互作用，导致两种恶性表型（侵袭和MDR）的同时表达和调节。
Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of morbidity and mortality from cancer. For more than two decades, these two important but not clearly related aspects in the biology of cancer have been extensively studied. Specifically, P-glycoprotein and CD44 have been characterized and are known to be determinants of multidrug resistance (MDR) and metastases. Despite this body of knowledge, few reports have linked the two phenotypes and only recently have there been reasons to suspect a direct connection. In this report, we show that a novel physical and genetic interaction between CD44s and P-glycoprotein is in part responsible for the correlation between MDR and invasive potential in cancer cells. P-glycoprotein-specific substrates that interfere with its function reduced in vitro invasion, migration, and the physical colocalization of CD44s and P-glycoprotein. CD44 expression in sensitive cells promoted the expression of P-glycoprotein and the MDR phenotype. RNA interference of MDR1 inhibited the rate of cell migration. These data indicate that there is a close interaction between CD44 and P-glycoprotein that results in the concurrent expression and modulation of two malignant phenotypes, invasion and MDR.