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首页> 外文期刊>Proteome science >Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line
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Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line

机译：比较蛋白质组学分析表明eEF2是MDA-MB-231转移性乳腺癌细胞系中PI3Kγ的新靶标

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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 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. Results 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. Conclusions Our data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.
机译：背景技术癌细胞迁移是乳腺肿瘤浸润和转移的根本要求。已显示胰岛素样生长因子1酪氨酸激酶受体（IGF-1R）和趋化因子G蛋白偶联受体CXCR4在乳腺癌转移中起重要作用。我们以前的研究表明，IGF-1R可以通过人MDA-MB-231转移性乳腺癌细胞系中的物理缔合来激活CXCR4，这在IGF-I诱导的这些细胞迁移中起关键作用。在本研究中，我们使用药理抑制作用和RNAi来鉴定PI3Kγ是MDA-MB-231细胞中受体反式激活下游的重要迁移信号分子。为了通过IGF-I反式激活CXCR4来鉴定PI3Kγ调控的蛋白质，我们采用了2-D荧光差异凝胶电泳（DIGE）进行了比较蛋白质组学方法，并通过质谱鉴定了蛋白质。结果这些实验确定了由IGF-1激活IGF-1R-CXCR4异二聚体后，真核生物延伸因子2（eEF2）是PI3Kγ的新型下游靶标。进一步的分析表明，eEF2在MDA-MB-231细胞中响应IGF-I磷酸化，这取决于PI3Kγ活性。结论我们的数据暗示PI3Kγ通过调节eEF2的磷酸化在促进细胞迁移中具有新作用。

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