title: A Novel NHERF1 Mutation in Human Breast Cancer Inactivates Inhibition by NHERF1 Protein in EGFR Signaling.
abstract: BACKGROUND
  Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins. We recently identified a novel NHERF1 mutation (E43G) in breast tumours.
  
  
  METHODS
  The candidates of NHERF1 mutation were identified in breast cancer tissues by polymerase chain reaction and DNA sequencing. Wild-type NHERF1 and E43G mutation were expressed in NHERF1-knockdown cells (MCF7ΔNHERF1) and low-NHERF1-expressing cells (SKMES-1). The effects of mutated NHERF1 on cell functions were examined using in vitro methods. Glutathione S-transferase pull-down assays and western blotting were performed to study the effects of NHERF1 mutation on its interaction with cancer-related proteins.
  
  
  RESULTS
  Compared to wild-type NHERF1, expression of the mutated NHERF1 failed to suppress malignant traits in cancer cells, attenuated interaction of NHERF1 protein with epidermal growth factor receptor (EGFR), and inactivated its inhibition of EGF-induced Akt and extracellular regulated protein kinases (ERK) activation.
  
  
  CONCLUSIONS
  The results show the causal role of NHERF1 in the regulation of the EGFR pathway and the progression of breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Guifang
authors.initials: G
authors.lastname: DU
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China chengs@ccmu.edu.cn jq_he@ccmu.edu.cn.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory of Cancer & Metastasis Research, Capital Medical University, Beijing, P.R. China chengs@ccmu.edu.cn jq_he@ccmu.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Cheng
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000819:agonists / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: EGFR; NHERF1 mutation; breast cancer