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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 ORCID: https://orcid.org/0000-0002-3283-1111 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: 28 Oct 2022 09:27
URI: https://orca.cardiff.ac.uk/id/eprint/74600

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