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

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-sma...

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Autores principales: Che, Ting-Fang, Lin, Ching-Wen, Wu, Yi-Ying, Chen, Yu-Ju, Han, Chia-Li, Chang, Yih-leong, Wu, Chen-Tu, Hsiao, Tzu-Hung, Hong, Tse-Ming, Yang, Pan-Chyr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741934/
https://www.ncbi.nlm.nih.gov/pubmed/26497368
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author Che, Ting-Fang
Lin, Ching-Wen
Wu, Yi-Ying
Chen, Yu-Ju
Han, Chia-Li
Chang, Yih-leong
Wu, Chen-Tu
Hsiao, Tzu-Hung
Hong, Tse-Ming
Yang, Pan-Chyr
author_facet Che, Ting-Fang
Lin, Ching-Wen
Wu, Yi-Ying
Chen, Yu-Ju
Han, Chia-Li
Chang, Yih-leong
Wu, Chen-Tu
Hsiao, Tzu-Hung
Hong, Tse-Ming
Yang, Pan-Chyr
author_sort Che, Ting-Fang
collection PubMed
description 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.
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spelling pubmed-47419342016-03-17 Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC Che, Ting-Fang Lin, Ching-Wen Wu, Yi-Ying Chen, Yu-Ju Han, Chia-Li Chang, Yih-leong Wu, Chen-Tu Hsiao, Tzu-Hung Hong, Tse-Ming Yang, Pan-Chyr Oncotarget Research Paper 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. Impact Journals LLC 2015-10-19 /pmc/articles/PMC4741934/ /pubmed/26497368 Text en Copyright: © 2015 Che et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Che, Ting-Fang
Lin, Ching-Wen
Wu, Yi-Ying
Chen, Yu-Ju
Han, Chia-Li
Chang, Yih-leong
Wu, Chen-Tu
Hsiao, Tzu-Hung
Hong, Tse-Ming
Yang, Pan-Chyr
Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title_full Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title_fullStr Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title_full_unstemmed Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title_short Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC
title_sort mitochondrial translocation of egfr regulates mitochondria dynamics and promotes metastasis in nsclc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741934/
https://www.ncbi.nlm.nih.gov/pubmed/26497368
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