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

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. The inhibition of energy production in lung cancer tumors may help prevent metastasis due to drug-resistant cancer cells. A few cells in lung cancer tumors become resistant to chemotherapy, meaning that they can trigger relapse and metastasis (the spread of the disease to other organs) following treatment. Hyonchol Jang at the National Cancer Center, Republic of Korea, and co-workers investigated the metabolic differences between these drug-resistant cells and other cancer cells in the hope that these differences could be exploited to tackle metastasis. Genes associated with mitochondria, intracellular structures responsible for energy production, were over-expressed in the drug-resistant cells, enhancing their ability to migrate and invade. When Jang's team inhibited mitochondrial activity, the cells' ability to migrate to other organs was dramatically reduced. Such inhibition could help prevent drug-resistant cell metastasis in lung cancer.