以能量觀點探討表皮生長因子受體之活化對粒線體增生以及癌細胞存活之影響

Abstract

The over-expression of epidermal growth factor receptor (EGFR) has been observed in many cancer types including lung carcinoma. Since EGFR signaling significantly enhances cell growth and survival, several EGFR tyrosine kinase inhibitors (TKI) have been developed to specifically shut down EGFR signaling pathway. However, drug resistance occurs in most cases resulting from the secondary EGFR mutations. TKI-resistant EGFR mutation has been the major problem against TKI-based therapy. Since EGFR activation promotes tumor survival and proliferation, elevated energy supply must be achieved to meet such activities. Previous studies in our lab had found that the direct over-expression of MMP7 can induce mitochondria proliferation. To find the upstream regulator of MMP7, in this thesis we observed that the amount of MMP7 and mitochondria increased after EGF stimulation in NSCLC cell line CL1-0. Different EGFR mutants also possessed different mitochondria induction abilities, and the levels of MMP7 expression were also proportional to mitochondria content. Based on these findings, we treated these cell lines with the mitochondria ATP synthase inhibitor citreoviridin to see the cell viability differences. As expected, cells with higher mitochondria abundancy were more sensitive to citreoviridin, implying that the induction of mitochondria proliferation by EGFR may shift the cell metabolism status to be more mitochondria-dependent. In this study, we established a positive relationship between EGFR, MMP7 and mitochondria and also provided an energy point of view toward EGFR related cancer treatment.