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 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.
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.
Guifang
G
Du
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.
Yanan
Y
Gu
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.
Chengcheng
C
Hao
Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing 100069, China.|Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Zhu
Z
Yuan
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.
Junqi
J
He
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.|Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Wen G
WG
Jiang
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.
Shan
S
Cheng
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009154:Mutation; D054731:PDZ Domains / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism*
D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor
NHERF1; PDZ; breast cancer; cellular distribution; mutation