Du Guifang, Gu Yanan, Hao Chengcheng, Yuan Zhu, He Junqi, Jiang Wen G, Cheng Shan
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China.
Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.
Oncotarget. 2016 May 17;7(20):29440-53. doi: 10.18632/oncotarget.8751.
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.
最近有研究表明钠氢交换调节因子1（NHERF1）的异位表达具有致癌作用。在此，我们发现与低级别相比，NHERF1在高级别中表达上调。NHERF1表达增加与预后不良和生存率低相关。癌细胞核中的NHERF1表达高于相邻的非乳腺上皮细胞。在人类乳腺癌组织中鉴定出一种新的突变，即NHERF1 Y24S，并且显示其对应于NHERF1的PDZ-I结构域中的一个保守残基。NHERF1的PDZ-I结构域的截短和突变增加了NHERF1蛋白的核分布，并且这种重新分布与乳腺癌细胞的恶性表型相关，包括生长、迁移和粘附。目前的结果表明，由PDZ-I结构域的截短或关键位点突变所决定的NHERF1蛋白核分布介导了NHERF1在乳腺癌进展中的作用。
