Low‐expression of E‐cadherin in leukaemia cells causes loss of homophilic adhesion and promotes cell growth

Low‐expression of E‐cadherin in leukaemia cells causes loss of homophilic adhesion and promotes cell growth
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白血病细胞中 E-钙粘蛋白的低表达导致同亲粘附丧失并促进细胞生长

DOI:
10.1042/cbi20100456
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发表时间:
2011
影响因子:
3.9
通讯作者:
Jianxiang Wang
Jianxiang Wang
中科院分区:
生物学4区
文献类型:
--
作者:
Q. Rao;Ji;Ji;K. Tang;Yan;Min Wang;H. Xing;Z. Tian;Jianxiang Wang

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E-钙粘蛋白(上皮钙粘蛋白)属于钙依赖性粘附分子超家族,与造血祖细胞和骨髓基质细胞的相互作用有关。白血病细胞对骨髓基质的粘附能力受损,表明白血病微环境中可能存在由粘附分子控制的粘附机制的破坏。我们以前发现,与正常骨髓单个核细胞相比,E‐钙粘蛋白在原发性急性白血病细胞中表达较低。在这项研究中,我们研究了低E‐cadherin表达在白血病细胞行为中的功能重要性,并研究了其在白血病细胞与基质细胞异常相互作用中的作用。在白血病细胞中通过去甲基化剂恢复E-钙粘蛋白的表达后,E-钙粘蛋白特异性粘附增强。此外,siRNA(小干扰RNA)介导的Raji细胞中E-钙粘蛋白沉默导致细胞嗜同性粘附减少,细胞增殖和集落形成增强。这些结果表明,E‐cadherin的低表达有助于白血病细胞的旺盛生长和转化能力。
E‐cadherin (epithelial cadherin) belongs to the calcium‐dependent adhesion molecule superfamily and is implicated in the interactions of haematopoietic progenitors and bone marrow stromal cells. Adhesion capacity to bone marrow stroma was impaired for leukaemia cells, suggesting that a breakdown of adhesive mechanisms governed by an adhesion molecule may exist in leukaemic microenvironment. We previously found that E‐cadherin was low expressed in primary acute leukaemia cells compared with normal bone marrow mononuclear cells. In this study, we investigate the functional importance of low E‐cadherin expression in leukaemia cell behaviours and investigate its effects in the abnormal interaction of leukaemic cells with stromal cells. After expression of E‐cadherin was restored by a demethylating agent in leukaemia cells, E‐cadherin‐specific adhesion was enhanced. Additionally, siRNA (small interfering RNA)‐mediated silencing of E‐cadherin in Raji cells resulted in a reduction of cell homophilic adhesion and enhancement of cell proliferation and colony formation. These results suggest that low expression of E‐cadherin contributes to the vigorous growth and transforming ability of leukaemic cells.
DOI: --
发表时间: 2000-11
期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子: --
作者:
P. Corn;B. Smith;Emily S. Ruckdeschel;Donna B. Douglas;S. Baylin;J. Herman
通讯作者: P. Corn;B. Smith;Emily S. Ruckdeschel;Donna B. Douglas;S. Baylin;J. Herman