Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC

Ting Fang Che, Ching Wen Lin, Yi Ying Wu, Yu Ju Chen, Chia Li Han, Yih leong Chang, Chen Tu Wu, Tzu Hung Hsiao, Tse Ming Hong, Pan Chyr Yang

研究成果: 雜誌貢獻文章

29 引文 斯高帕斯(Scopus)

摘要

Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.

原文英語
頁(從 - 到)37349-37366
頁數18
期刊Oncotarget
6
發行號35
DOIs
出版狀態已發佈 - 2015

ASJC Scopus subject areas

  • Oncology

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    Che, T. F., Lin, C. W., Wu, Y. Y., Chen, Y. J., Han, C. L., Chang, Y. L., Wu, C. T., Hsiao, T. H., Hong, T. M., & Yang, P. C. (2015). Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC. Oncotarget, 6(35), 37349-37366. https://doi.org/10.18632/oncotarget.5736