https://scholars.lib.ntu.edu.tw/handle/123456789/473779| Title: | Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC | Authors: | Che T.-F. Lin C.-W. Wu Y.-Y. Chen Y.-J. Han C.-L. YIH-LEONG CHANG CHEN-TU WU Hsiao T.-H. Hong T.-M. PAN-CHYR YANG |
Issue Date: | 2015 | Publisher: | Impact Journals LLC | Journal Volume: | 6 | Journal Issue: | 35 | Start page/Pages: | 37349-37366 | Source: | Oncotarget | Abstract: | 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84947788132&doi=10.18632%2foncotarget.5736&partnerID=40&md5=aa13958dde8da024d466394fb3ac0453 https://scholars.lib.ntu.edu.tw/handle/123456789/473779 |
ISSN: | 1949-2553 | DOI: | 10.18632/oncotarget.5736 | SDG/Keyword: | adenosine triphosphate; epidermal growth factor; epidermal growth factor receptor; mitochondrial protein; mitofusin 1; tyrosine; carrier protein; EGFR protein, human; epidermal growth factor; epidermal growth factor receptor; guanosine triphosphatase; Mfn1 protein, human; animal cell; animal experiment; animal model; animal tissue; Article; biosynthesis; cancer patient; cancer survival; cell motility; cohort analysis; controlled study; disease activity; human; human tissue; in vitro study; in vivo study; intracellular transport; lamellipodium; lung cancer cell line; lymph node metastasis; male; mitochondrion; molecular dynamics; mouse; non small cell lung cancer; nonhuman; overall survival; phenotype; primary tumor; protein expression; protein function; protein localization; protein polymerization; protein protein interaction; protein transport; proteomics; regulatory mechanism; tumor invasion; upregulation; agonists; animal; cell motion; dose response; drug effects; endocytosis; energy metabolism; enzymology; genetic transfection; genetics; genotype; lung tumor; lymph node metastasis; metabolism; mitochondrial dynamics; mitochondrion; non small cell lung cancer; nonobese diabetic mouse; pathology; procedures; protein transport; SCID mouse; secondary; signal transduction; time factor; tumor cell line; xenograft; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Endocytosis; Energy Metabolism; Epidermal Growth Factor; Genotype; GTP Phosphohydrolases; Heterografts; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Mice, Inbred NOD; Mice, SCID; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membrane Transport Proteins; Phenotype; Protein Transport; Proteomics; Receptor, Epidermal Growth Factor; Signal Transduction; Time Factors; Transfection [SDGs]SDG3 |
| Appears in Collections: | 病理學科所 |
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