Characterization of a beta-catenin nuclear localization defect in MCF-7 breast cancer cells
Characterization of a beta-catenin nuclear localization defect in MCF-7 breast cancer cells
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DOI：
10.1016/j.yexcr.2016.01.020
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发表时间：
2016-02-15
影响因子：
3.7
通讯作者：
Henderson, Beric R.
中科院分区：
文献类型：
--
作者：
Jamieson, Cara;Mills, Kate M.;Henderson, Beric R.
β-连环蛋白在将Wnt信号从质膜传递到细胞核中起着关键作用。在这里，我们描述了一种不同寻常的亚细胞分布的β-连环素在MCF-7乳腺癌细胞中的分布，其中β-连环素定位于细胞质和细胞膜，但在WNT治疗后不典型地重新定位到细胞核。Wnt或Wnt激动剂LiCl不能诱导β-catenin的核定位不是由于核运输缺陷，因为运输机制是完整的，而且异位GFP-β-catenin在活细胞中显示出快速的核进入。这种错误定位的原因是β-连环蛋白的滞留从细胞核转移到细胞质。核滞留的减少是由于淋巴增强因子/T细胞因子(Lef/Tcf)转录因子的异常低表达所致。Lef-1或TCF4表达的重建挽救了β-连环蛋白在Wnt处理细胞中的核定位。在细胞质中，β-连环蛋白积聚在循环内小体、高尔基体和β-COP阳性的辅瘤复合体中。在WNT治疗后，与内体的外周联系减弱，潜在地将β-连环蛋白释放到细胞质中以供核进入。我们认为，在MCF-7和其他乳腺癌细胞中，β-连环蛋白除了在细胞核中发挥反式激活作用外，还可能参与细胞质功能，如内质网高尔基体转运。(C)2016 Elsevier Inc.保留所有权利。
Beta-catenin plays a key role in transducing Wnt signals from the plasma membrane to the nucleus. Here we characterize an unusual subcellular distribution of beta-catenin in MCF-7 breast cancer cells, wherein beta-catenin localizes to the cytoplasm and membrane but atypically did not relocate to the nucleus after Wnt treatment. The inability of Wnt or the Wnt agonist LiCl to induce nuclear localization of beta-catenin was not due to defective nuclear transport, as the transport machinery was intact and ectopic GFP-beta-catenin displayed rapid nuclear entry in living cells. The mislocalization is explained by a shift in the retention of beta-catenin from nucleus to cytoplasm. The reduced nuclear retention is caused by unusually low expression of lymphoid enhancer factor/T-cell factor (LEF/TCF) transcription factors. The reconstitution of LEF-1 or TCF4 expression rescued nuclear localization of beta-catenin in Wnt treated cells. In the cytoplasm, beta-catenin accumulated in recycling endosomes, golgi and beta-COP-positive coatomer complexes. The peripheral association with endosomes diminished after Wnt treatment, potentially releasing beta-catenin into the cytoplasm for nuclear entry. We propose that in MCF-7 and perhaps other breast cancer cells, beta-catenin may contribute to cytoplasmic functions such as ER-golgi transport, in addition to its transactivation role in the nucleus. (C) 2016 Elsevier Inc. All rights reserved.