Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating theVE-cadherin/β-catenin signal
Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating theVE-cadherin/β-catenin signal
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DOI：
10.1016/j.leukres.2014.09.012
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发表时间：
2014-12-01
影响因子：
2.7
通讯作者：
Xu, Kai-Lin
中科院分区：
文献类型：
--
作者：
Chen, Chong;Zhang, Huan-Xin;Xu, Kai-Lin
β-连环蛋白是白血病干细胞维持和耐药的关键调节因子。在此，我们研究了基质细胞介导的VE-钙粘蛋白-β-连环蛋白信号在伊马替尼治疗过程中对Ph+白血病细胞的保护作用。我们发现基质细胞可以脱敏伊马替尼，上调Ph+白血病细胞(K562和SUP-B15)VE-cadherin的表达，从而进一步稳定和激活β-catenin。用shRNA敲除VE-cadherin可减少β-catenin蛋白的表达，并部分恢复Ph+白血病细胞对伊马替尼的敏感性，提示VE-cadherin是治疗Ph+白血病的一个潜在靶点。(C)2014爱思唯尔有限公司。保留所有权利。
beta-Catenin is a key regulator of leukemia stem cell maintenance and drug resistance. Herein, we investigated the protective effects of the stromal cell-mediated VE-cadherin-beta-catenin signal on Ph+ leukemia cells during imatinib treatment. We found stromal cells could desensitize imatinib and up-regulate VE-cadherin expression on Ph+ leukemia cells (K562 and SUP-B15 cells), which further stabilized and activated beta-catenin. Knockdown of VE-cadherin with shRNA diminished the beta-catenin protein and partly resensitized Ph+ leukemia cells to imatinib despite the presence of stromal cells, suggesting VE-cadherin is a potential target in the treatment of Ph+ leukemia. (C) 2014 Elsevier Ltd. All rights reserved.