title: Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China; Capital Medical University-Cardiff University Joint Centre for Biomedical Research, Capital Medical University, Beijing 100069, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Duiping
authors.initials: D
authors.lastname: Feng
authors.forename: Longyan
authors.initials: L
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.forename: Shuai
authors.initials: S
authors.lastname: Zheng
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.forename: Shuhui
authors.initials: S
authors.lastname: Wang
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.forename: Junqi
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D020797:Receptor, Platelet-Derived Growth Factor beta; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Breast cancer; EBP50; NHERF1; PDGFR; PDZ; PTEN