PMID- 26977012 OWN - NLM STAT- MEDLINE DCOM- 20161107 LR - 20181202 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 36 IP - 3 DP - 2016 Mar TI - A Novel NHERF1 Mutation in Human Breast Cancer Inactivates Inhibition by NHERF1 Protein in EGFR Signaling. PG - 1165-73 AB - 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. MATERIALS AND 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 (MCF7DeltaNHERF1) 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. CONCLUSION: The results show the causal role of NHERF1 in the regulation of the EGFR pathway and the progression of breast cancer. CI - Copyright(c) 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - DU, Guifang AU - DU G AD - 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. FAU - Hao, Chengcheng AU - Hao C AD - 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. FAU - Gu, Yanan AU - Gu Y AD - 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. FAU - Wang, Zhiyan AU - Wang Z AD - 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. FAU - Jiang, Wen G AU - Jiang WG AD - 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. FAU - He, Junqi AU - He J AD - 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. FAU - Cheng, Shan AU - Cheng S AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Phosphoproteins) RN - 0 (Sodium-Hydrogen Exchangers) RN - 0 (sodium-hydrogen exchanger regulatory factor) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Breast Neoplasms/genetics/*metabolism MH - Cell Adhesion MH - Cell Movement MH - Cell Proliferation MH - Enzyme Activation MH - Epidermal Growth Factor/pharmacology MH - ErbB Receptors/agonists/*metabolism MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Humans MH - MCF-7 Cells MH - Male MH - *Mutation MH - Neoplasm Invasiveness MH - Phenotype MH - Phosphoproteins/genetics/*metabolism MH - Protein Binding MH - Proto-Oncogene Proteins c-akt/metabolism MH - *Signal Transduction/drug effects MH - Sodium-Hydrogen Exchangers/genetics/*metabolism MH - Transfection OTO - NOTNLM OT - EGFR OT - NHERF1 mutation OT - breast cancer EDAT- 2016/03/16 06:00 MHDA- 2016/11/08 06:00 CRDT- 2016/03/16 06:00 PHST- 2016/03/16 06:00 [entrez] PHST- 2016/03/16 06:00 [pubmed] PHST- 2016/11/08 06:00 [medline] AID - 36/3/1165 [pii] PST - ppublish SO - Anticancer Res. 2016 Mar;36(3):1165-73.