Breast cancer-derived K172N,D301V mutations abolish Na/H exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling |
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| Authors: | Shan Cheng Yang Li Ying Yang Duiping Feng Longyan Yang Qian Ma Shuai Zheng Ran Meng Shuhui Wang Songlin Wang Wen G. Jiang Junqi He |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China;2. Proteomic Research Center, Capital Medical University, Beijing 100069, China;3. Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100069, China;4. Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China;5. Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Capital Medical University, Beijing 100069, China;6. Metastasis and Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK |
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| Abstract: | Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression. |
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| Keywords: | Breast cancer NHERF1 PDZ PDGFR PTEN EBP50 |
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