title: A Novel NHERF1 Mutation in Human Breast Cancer and Effects on Malignant Progression.
abstract: Na+/H+exchanger regulatory factor 1 (NHERF1) has been reported to interact with post-synaptic density protein/Drosophila disc large tumour suppressor/zonula occludens 1 protein (PDZ) binding proteins by its two PDZ domains. These associations have effects on cellular signal transductions. NHERF1 has also been indicated as a cancer-related gene in several solid tumour types. We identified a novel mutation (A190D), of the PDZ2 domain of NHERF1 in breast cancer tissues. NHERF1 A190D mutation abolished NHERF1 modulation of proliferation and migration. In this study, we found that NHERF1 A190D mutation increased nuclear localisation of the protein compared to wild-type NHERF1. It has been reported that YES-associated protein (YAP) interacts with NHERF1. Here we found that NHERF1 A190D mutation increased the binding affinity between NHERF1 and YAP, which inhibited the phosphorylation of YAP. These data suggest that wild-type NHERF1 acts as a tumour suppressor, while NHERF1 A190D mutation abolishes the tumour-suppressive effect in cancer cells, due to A190D mutation-mediated nuclear NHERF1 translocation and induction of YAP phosphorylation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical School, Capital Medical University, Beijing, P.R. China.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical School, Capital Medical University, Beijing, P.R. China.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer 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, Basic Medical School, Capital Medical University, Beijing, P.R. China.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical School, Capital Medical University, Beijing, P.R. China.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Si
authors.affiliation: Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical School, Capital Medical University, Beijing, P.R. China JiangW@cardiff.ac.uk chengs@ccmu.edu.cn jq_he@ccmu.edu.cn.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medical School, Capital Medical University, Beijing, P.R. China JiangW@cardiff.ac.uk chengs@ccmu.edu.cn jq_he@ccmu.edu.cn.|Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cancer Institute of Capital Medical University, Capital Medical University, Beijing, P.R. China JiangW@cardiff.ac.uk chengs@ccmu.edu.cn jq_he@ccmu.edu.cn.|Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Capital Medical University, Beijing, P.R. China.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer 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
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002465:Cell Movement; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009154:Mutation; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C093376:sodium-hydrogen exchanger regulatory factor
keywords: NHERF1 mutation; breast cancer; progression