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Breast cancer‐derived K172N, D301V mutations abolish Na + /H + exchanger regulatory factor 1 inhibition of platelet‐derived growth factor receptor signaling
Author(s) -
Cheng Shan,
Li Yang,
Yang Ying,
Feng Duiping,
Yang Longyan,
Ma Qian,
Zheng Shuai,
Meng Ran,
Wang Shuhui,
Wang Songlin,
Jiang Wen G.,
He Junqi
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.026
Subject(s) - cancer research , chemistry , signal transduction , growth factor , receptor , microbiology and biotechnology , biology , biochemistry
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.