Mitochondrial Translocation of EGFR Regulates Mitochondrial Dynamics and Promotes Cancer Metastasis in NSCLC
Date Issued
2015
Date
2015
Author(s)
Che, Ting-Fang
Abstract
Dysfunction of the mitochondria, the versatile cellular organelles, is shown to be related to cancer progression. In the present study, the iTRAQ was exploited to analyze mitochondrial proteomics of lung cancer cell lines with variable migration abilities. We found that EGFR is highly expressed in highly invasive lung cancer cell mitochondria. We demonstrated that the mitochondrial translocation of EGFR by EGF induces mitochondrial fission, and upregulates energy production, causes mitochondrial redistribution in the lamellipodia, and enhances cell motility. Besides, EGFR can still regulate mitochondria dynamics and cell motility, independent of its phosphorylation status. Furthermore, EGFR was found to interact with mitofusion1 (Mfn1), a mitochondrial protein which causes mitochondria fusion by polymerization to regulate mitochondrial dynamics. Overexpressing Mfn1 significantly reversed the phenotypes resulted from mitochondrial translocation of EGFR. Corresponding to the above finding, the EGFR expression in cytosol rather than on the cell surface is reversely correlated to the overall survival of NSCLC patients. Notably, the cytosolic EGFR expression levels in the lymph node-locating tumor cells are higher than that of the paired primary tumor sites. Collectively, our results show that mitochondrial EGFR plays an important role on mitochondrial morphology, energy production and distributions, which further promotes cellular motility. Accordingly, mitochondrial EGFR expression is involved in cancer invasion and can serve as a diagnostic marker for predicting NSCLC malignancy.
Subjects
lung cancer
EGFR
mitochondria
NSCLC
SDGs
Type
thesis
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