FZD7 regulates BMSCs-mediated protection of CML cells.
FZD7 regulates BMSCs-mediated protection of CML cells.
复制标题
FZD7 调节 BMSC 介导的 CML 细胞保护。
DOI：
10.18632/oncotarget.6742
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发表时间：
2016-02-02
期刊：
影响因子：
--
通讯作者：
Ji C
中科院分区：
文献类型：
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作者：
Liu N;Zang S;Liu Y;Wang Y;Li W;Liu Q;Ji M;Ma D;Ji C
尽管伊马替尼（IM）治疗有效，但慢性粒细胞白血病（CML）仍然是一种无法治愈的疾病。一些患者由于IM抵抗而变得难治。骨髓间充质干细胞（BMSCs）在促进CML细胞对IM治疗的抵抗中起作用。然而，详细的分子机制在很大程度上仍然未知。在本研究中，我们发现骨髓间充质干细胞可增加CML细胞中FZD 7的表达，并激活Wnt/β-catenin信号通路。CML患者骨髓间充质干细胞可促进CML细胞增殖，增强K562细胞的耐药性，并上调FZD 7的表达。shRNA拮抗FZD 7表达可显著抑制CML细胞与BMSCs细胞共培养的增殖并增加IM敏感性。我们的研究结果表明，FZD 7，参与经典的Wnt信号通路，在介导骨髓基质细胞依赖的CML细胞的保护中起着关键作用，并可能提供一个新的治疗CML的目标。
Inspite of effective treatment with imatinib (IM), chronic myeloid leukemia (CML) is still an incurable disease. Some patients became refractory because of IM resistance. Bone marrow mesenchymal stem cells (BMSCs) have been implicated a role in promoting CML cells' resistance against IM treatment. The detailed molecular mechanisms, however, remain largely unknown. In this study, we found that BMSCs increased the expression of FZD7 and activated Wnt/β-catenin signaling pathway in CML cells. BMSCs from CML patients showed increased efficiency to accelerate CML cell proliferation, enhance the drug resistance of K562 cells and up-regulate the expression of FZD7. Antagonism of FZD7 expression by shRNA significantly suppressed proliferation and increased IM sensitivity of CML cells co-cultured with BMSCs cells. Our findings suggest that FZD7, involved in canonical Wnt signaling pathway, plays a critical role in mediating BMSCs-dependent protection of CML cells, and potentially provide a novel therapeutic target for CML.