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Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

Authors
 Ji Hoon Jeon  ;  Dong Keon Kim  ;  Youngmi Shin  ;  Hee Yeon Kim  ;  Bomin Song  ;  Eun Young Lee  ;  Jong Kwang Kim  ;  Hye Jin You  ;  Heesun Cheong  ;  Dong Hoon Shin  ;  Seong-Tae Kim  ;  Jae-Ho Cheong  ;  Soo Youl Kim  ;  Hyonchol Jang 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.48(12) : e277, 2016 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2016
MeSH
Adenocarcinoma/diagnosis ; Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology* ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects ; Cisplatin/pharmacology ; Drug Resistance, Neoplasm* ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology* ; Mitochondria/drug effects ; Mitochondria/pathology* ; Neoplasm Invasiveness/pathology* ; Prognosis
Abstract
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.
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DOI
10.1038/emm.2016.129
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166044
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