%0 Journal Article
%T Comparative proteomic analysis implicates eEF2 as a novel target of PI3K¦Ã in the MDA-MB-231 metastatic breast cancer cell line
%A Niu Meizhi
%A Klingler-Hoffmann Manuela
%A Brazzatti Julie A
%A Forbes Briony
%J Proteome Science
%D 2013
%I BioMed Central
%R 10.1186/1477-5956-11-4
%X Background Cancer cell migration is fundamentally required for breast tumour invasion and metastasis. The insulin-like growth factor 1 tyrosine kinase receptor (IGF-1R) and the chemokine G-protein coupled receptor, CXCR4 have been shown to play an important role in breast cancer metastasis. Our previous study has shown that IGF-1R can transactivate CXCR4 via a physical association in the human MDA-MB-231 metastatic breast cancer cell line and that this plays a key role in IGF-I-induced migration of these cells. In the present study we used pharmacological inhibition and RNAi to identify PI3K¦Ã as an important migration signalling molecule downstream of receptor transactivation in MDA-MB-231 cells. To identify PI3K¦Ã-regulated proteins upon transactivation of CXCR4 by IGF-I, we undertook a comparative proteomics approach using 2-D- Fluorescence Difference Gel Electrophoresis (DIGE) and identified the proteins by mass spectrometry. Results These experiments identified eukaryotic elongation factor 2 (eEF2) as a novel downstream target of PI3K¦Ã after activation of the IGF-1R-CXCR4 heterodimer by IGF-I. Further analysis demonstrated that eEF2 is phosphorylated in MDA-MB-231 cells in response to IGF-I and that this is dependent on PI3K¦Ã activity. Conclusions Our data imply a novel role for PI3K¦Ã in facilitating cell migration by regulating phosphorylation of eEF2.
%K Receptor transactivation
%K Cell migration
%K IGF-I
%K CXCR4
%K PI3K¦Ã
%K eEF2
%K 2D-DIGE
%U http://www.proteomesci.com/content/11/1/4