Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line

Proteome Science

Research

Manuela Klingler-Hoffmann¹  Briony Forbes¹  Meizhi Niu¹  Peter Hoffmann¹  Shaun R McColl¹  Chareeporn Akekawatchai²  Julie A Brazzatti³ 

[1] School of Molecular and Biomedical Science, University of Adelaide, 5005, Adelaide, SA, Australia;School of Molecular and Biomedical Science, University of Adelaide, 5005, Adelaide, SA, Australia;Department of Medical Technology, Thammasat University, 121212, Patumtani, Thailand;School of Molecular and Biomedical Science, University of Adelaide, 5005, Adelaide, SA, Australia;Immunology Group, Paterson Institute for cancer research, The University of Manchester, M20 4BX, Manchester, England;

关键词: Receptor transactivation;    Cell migration;    IGF-I;    CXCR4;    PI3Kγ;    eEF2;    2D-DIGE;   

DOI  :  10.1186/1477-5956-11-4

 received in 2012-08-06, accepted in 2012-12-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCancer 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 PI3Kγ as an important migration signalling molecule downstream of receptor transactivation in MDA-MB-231 cells. To identify PI3Kγ-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.ResultsThese experiments identified eukaryotic elongation factor 2 (eEF2) as a novel downstream target of PI3Kγ 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 PI3Kγ activity.ConclusionsOur data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.

【 授权许可】

Unknown   
© Niu et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.