In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1138-1138
Abstract:
Na+/H+ exchanger regulatory factor 1 (NHERF1, also known as EBP50) is a scaffold protein known to interact with a number of target proteins, including cancer-related proteins such as phosphatase and tensin homolog deleted on chromosome 10 (PTEN), neurofibromatosis 2, spleen tyrosine kinase, platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and β-catenin. This suggests a possible function of NHERF1 as a negative tumor regulator. Several lines of evidence have suggested that NHERF1 is involved in carcinogenesis. However, the mechanisms by which NHERF1 plays a role in breast cancer have not yet been clearly defined. Three point mutations in nherf1 (K172N, R180W, and D301V) were recently identified in breast cancer cell lines or primary breast tumors. To gain more insight into the functional properties of NHERF1, wild-type (wt) and cancer-derived nherf1 mutations were introduced into a human non-small cell lung cancer cell line, SKMES-1. NHERF1-wt overexpression suppressed the malignant phenotypic characteristics of SKMES-1 cells, including cell proliferation, migration, and invasion. Three nherf1 mutations led to complete or partial loss of NHERF1 functions by affecting the formation of PTEN/NHERF1/PDGFRβ complex, attenuating NHERF1-mediated inhibition of PDGF-induced AKT and ERK activation, and abolishing the tumor suppressor effects mediated by NHERF1-wt. These results provide the first evidence of the functional consequences and signaling properties of breast cancer-derived nherf1 mutations, and suggest that these nherf1 mutations might play a causal role in tumor development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1138. doi:10.1158/1538-7445.AM2011-1138
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-1138
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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