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  • Title: A Novel NHERF1 Mutation in Human Breast Cancer Inactivates Inhibition by NHERF1 Protein in EGFR Signaling.
    Author: DU G, Hao C, Gu Y, Wang Z, Jiang WG, He J, Cheng S.
    Journal: Anticancer Res; 2016 Mar; 36(3):1165-73. PubMed ID: 26977012.
    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. 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 (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. CONCLUSION: The results show the causal role of NHERF1 in the regulation of the EGFR pathway and the progression of breast cancer.
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