title: Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity.
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.
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Dong Keon
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Bomin
authors.initials: B
authors.lastname: Song
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Jong Kwang
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: You
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Heesun
authors.initials: H
authors.lastname: Cheong
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.
authors.forename: Soo Youl
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang, Korea.|Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Hyonchol
authors.identifier: 0000-0003-1436-457X
authors.initials: H
authors.lastname: Jang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin