The cellular distribution of Na+/H+ exchanger regulatory factor 1 is determined by the PDZ-I domain and regulates the malignant progression of breast cancer.
The cellular distribution of Na+/H+ exchanger regulatory factor 1 is determined by the PDZ-I domain and regulates the malignant progression of breast cancer.
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Na/H交换调节因子1的细胞分布由PDZ-I结构域决定并调节乳腺癌的恶性进展
DOI：
10.18632/oncotarget.8751
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发表时间：
2016-05-17
期刊：
影响因子：
--
通讯作者：
Cheng S
中科院分区：
文献类型：
--
作者：
Du G;Gu Y;Hao C;Yuan Z;He J;Jiang WG;Cheng S
最近有人提出Na+/H+交换调节因子1 （NHERF1）异位表达的致癌作用。在这里，我们发现与低年级相比，NHERF1在高年级中上调。NHERF1表达升高与预后差、生存差相关。NHERF1在癌细胞细胞核中的表达高于相邻的非乳腺上皮细胞。一个新的突变，即NHERF1 Y24S，在人类乳腺癌组织中被发现，并显示对应于NHERF1的pdz - 1结构域的一个保守残基。NHERF1的pdz - 1结构域的截断和突变增加了NHERF1蛋白的核分布，这种重分布与乳腺癌细胞的恶性表型有关，包括生长、迁移和粘附。目前的研究结果表明，NHERF1在乳腺癌进展中的作用是由NHERF1蛋白的核分布介导的，由pdz - 1结构域的截断或关键位点突变决定。
The oncogenic role of ectopic expression of Na+/H+ exchanger regulatory factor 1 (NHERF1) was recently suggested. Here, we show that NHERF1 was upregulated in high grades compared with low grades. Increased NHERF1 expression was correlated with poor prognosis and poor survival. NHERF1 expression was higher in the nucleus of cancer cells than in contiguous non- mammary epithelial cells. A novel mutation, namely NHERF1 Y24S, was identified in human breast cancer tissues and shown to correspond to a conserved residue in the PDZ-I domain of NHERF1. Truncation and mutation of the PDZ-I domain of NHERF1 increased the nuclear distribution of the NHERF1 protein, and this redistribution was associated with the malignant phenotype of breast cancer cells, including growth, migration, and adhesion. The present results suggest a role for NHERF1 in the progression of breast cancer mediated by the nuclear distribution of the NHERF1 protein, as determined by the truncation or key site mutation of the PDZ-I domain.
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