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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Guifang Du1,2, Yanan Gu1,2, Chengcheng Hao1,2, Zhu Yuan2,3, Junqi He1,2, Wen G. Jiang1,2,4, Shan Cheng1,2
1Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
2Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China
3Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
4Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK
Shan Cheng, e-mail: [email protected]
Keywords: breast cancer, NHERF1, PDZ, cellular distribution, mutation
Received: September 28, 2015 Accepted: March 28, 2016 Published: April 15, 2016
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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