The 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.

中文翻译：

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对亚细胞EGFR相互作用基因组的分析显示hnRNP A3调节核EGFR的定位。

表皮生长因子受体（EGFR）的异常亚细胞移位和分布代表了非小细胞肺癌（NSCLC）中一种主要的但目前未被充分认识的癌症发展机制。在这项研究中，我们通过使用基于光谱计数的方法结合液相色谱-串联质谱法研究了EGFR的亚细胞相互作用组，以了解与NSCLC的肿瘤发生有关的相关蛋白网络。分别在来自NSCLC细胞系的胞质，线粒体和核级分中分别鉴定出总共54、77和63个EGFR相互作用蛋白。使用KEGG数据库对这些蛋白进行的途径分析表明，胞质和细胞核的EGFR相互作用蛋白分别与核糖体和剪接体途径有关，而线粒体的那些参与代谢丙酸酯，脂肪酸，缬氨酸，亮氨酸和异亮氨酸。发现一种选择的核EGFR相互作用蛋白hnRNP A3可以调节核EGFR的积累。hnRNP A3的下调减少了EGFR的核积累，并伴随着体内外肿瘤生长能力的降低。这些结果表明NSCLC细胞内EGFR的亚细胞转运和分布变化可能影响肿瘤进展。并且伴随着体外和体内肿瘤生长能力的降低。这些结果表明NSCLC细胞内EGFR的亚细胞转运和分布变化可能影响肿瘤进展。并且伴随着体外和体内肿瘤生长能力的降低。这些结果表明NSCLC细胞内EGFR的亚细胞转运和分布变化可能影响肿瘤进展。