Abstract
AbstractThe aberrant subcellular translocation and distribution of epidermal growth factor receptor (EGFR) represent a major yet currently underappreciated cancer development mechanism in non-small cell lung cancer (NSCLC). In this study, we investigated the subcellular interactome of EGFR by using a spectral counting-based approach combined with liquid chromatography–tandem mass spectrometry to understand the associated protein networks involved in the tumorigenesis of NSCLC. A total of 54, 77, and 63 EGFR-interacting proteins were identified specifically in the cytosolic, mitochondrial, and nuclear fractions from a NSCLC cell line, respectively. Pathway analyses of these proteins using the KEGG database shown that the EGFR-interacting proteins of the cytosol and nucleus are involved in the ribosome and spliceosome pathways, respectively, while those of the mitochondria are involved in metabolizing propanoate, fatty acid, valine, leucine, and isoleucine. A selected nuclear EGFR-interacting protein, hnRNP A3, was found to modulate the accumulation of nuclear EGFR. Downregulation of hnRNP A3 reduced the nuclear accumulation of EGFR, and this was accompanied by reduced tumor growth ability in vitro and in vivo. These results indicate that variations in the subcellular translocation and distribution of EGFR within NSCLC cells could affect tumor progression.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Molecular Biology
Reference56 articles.
1. Maemondo, M. et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 362, 2380–2388 (2010).
2. Lo, H. W. et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 7, 575–589 (2005).
3. Lo, H. W. Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications. Discov. Med. 10, 44–51 (2010).
4. Boerner, J. L., Demory, M. L., Silva, C. & Parsons, S. J. Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Mol. Cell. Biol. 24, 7059–7071 (2004).
5. Demory, M. L. et al. Epidermal growth factor receptor translocation to the mitochondria: regulation and effect. J. Biol. Chem. 284, 36592–36604 (2009).
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