Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2013-01-01
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| Series: | Proteome Science |
| Subjects: | |
| Online Access: | http://www.proteomesci.com/content/11/1/4 |
| _version_ | 1818934373771116544 |
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| author | Niu Meizhi Klingler-Hoffmann Manuela Brazzatti Julie A Forbes Briony Akekawatchai Chareeporn Hoffmann Peter McColl Shaun R |
| author_facet | Niu Meizhi Klingler-Hoffmann Manuela Brazzatti Julie A Forbes Briony Akekawatchai Chareeporn Hoffmann Peter McColl Shaun R |
| author_sort | Niu Meizhi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 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.</p> <p>Results</p> <p>These 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.</p> <p>Conclusions</p> <p>Our data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.</p> |
| first_indexed | 2024-12-20T05:03:15Z |
| format | Article |
| id | doaj.art-882ba9f33c7c477baff9b1a6074f9cee |
| institution | Directory Open Access Journal |
| issn | 1477-5956 |
| language | English |
| last_indexed | 2024-12-20T05:03:15Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Proteome Science |
| spelling | doaj.art-882ba9f33c7c477baff9b1a6074f9cee2022-12-21T19:52:29ZengBMCProteome Science1477-59562013-01-01111410.1186/1477-5956-11-4Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell lineNiu MeizhiKlingler-Hoffmann ManuelaBrazzatti Julie AForbes BrionyAkekawatchai ChareepornHoffmann PeterMcColl Shaun R<p>Abstract</p> <p>Background</p> <p>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 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.</p> <p>Results</p> <p>These 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.</p> <p>Conclusions</p> <p>Our data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.</p>http://www.proteomesci.com/content/11/1/4Receptor transactivationCell migrationIGF-ICXCR4PI3KγeEF22D-DIGE |
| spellingShingle | Niu Meizhi Klingler-Hoffmann Manuela Brazzatti Julie A Forbes Briony Akekawatchai Chareeporn Hoffmann Peter McColl Shaun R Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line Proteome Science Receptor transactivation Cell migration IGF-I CXCR4 PI3Kγ eEF2 2D-DIGE |
| title | Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line |
| title_full | Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line |
| title_fullStr | Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line |
| title_full_unstemmed | Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line |
| title_short | Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line |
| title_sort | comparative proteomic analysis implicates eef2 as a novel target of pi3kγ in the mda mb 231 metastatic breast cancer cell line |
| topic | Receptor transactivation Cell migration IGF-I CXCR4 PI3Kγ eEF2 2D-DIGE |
| url | http://www.proteomesci.com/content/11/1/4 |
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