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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

Cheng, S., Li, Y., Yang, Y., Feng, D., Yang, L., Ma, Q., Zheng, S., Meng, R., Wang, S., Wang, S., Jiang, Wen Guo and He, J. 2013. Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling. FEBS Letters 587 (20) , pp. 3289-3295. 10.1016/j.febslet.2013.08.026

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: Animals;BreastNeoplasms;CellLineTumor;CellProliferation;Cercopithecusaethiops;COSCells;Female;Humans;Mutation;Phosphoproteins;ProteinBinding;PTENPhosphohydrolase;ReceptorPlateletDerivedGrowthFactorbeta;Sodium-Hydrogen Antiporter
Additional Information: EMTREE drug terms: mitogen activated protein kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; platelet derived growth factor beta receptor; platelet derived growth factor receptor; protein kinase B; sodium proton exchange protein; sodium proton exchanger regulatory factor 1; unclassified drug EMTREE medical terms: article; breast cancer; cancer cell; cell invasion; cell migration; cell proliferation; complex formation; controlled study; enzyme activation; mutational analysis; point mutation; priority journal; protein expression; protein function; signal transduction; tumor growth Medline keywords: Breast cancer; EBP50; NHERF1; PDGFR; PDZ; PTEN Medline is the source for the MeSH terms of this document.
Publisher: Elsevier
ISSN: 0014-5793
Date of Acceptance: 26 August 2013
Last Modified: 11 Sep 2017 10:43
URI: http://orca.cf.ac.uk/id/eprint/74600

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