Single-Cell RNA Sequencing Suggests Oxidative Phosphorylation May Promote Breast Cancer Metastasis
Posted: Friday, May 15, 2020
Metastatic breast cancer cells switch from glycolysis and begin to use the mitochondrial metabolism, according to a new study published in Nature Cell Biology. In addition, the study discusses a method to identify the unique transcriptional program held by metastatic cells in patients with breast cancer. “This has important potential clinical implications, because it suggests that drugs targeting mitochondrial metabolism may have efficacy for preventing metastatic spread in patients,” said Devon A. Lawson, PhD, of the University of California Irvine in a press release from the school.
The research group used patient-derived xenografts from three patients and matched primary and metastatic cancer cells from nine mice combined with single-cell RNA sequencing to produce primary tumor and metastatic transcriptomes. Gene-expression analysis between primary and micrometastatic cells showed 330 differentially expressed genes, 116 of which are upregulated in micrometastatic cells.
The authors identified a shift in metabolism of micrometastatic cells by first finding an upregulation of genes associated with mitochondrial oxidative phosphorylation. This result contrasted with primary tumor cells, which express higher levels of genes associated with glycolysis. By using the fluorescent dye tetramethylrhodamine methyl ester, which accumulates in mitochondria, the researchers demonstrated that the mitochondrial membrane potential of micrometastatic cells was three times higher than that of primary tumor cells, indicating an increase in mitochondrial metabolism.
Lastly the authors compared the size of the primary tumor and the frequency of metastatic cells in mice treated with an inhibitor of oxidative phosphorylation and those who were not. They found that only the frequency of metastatic cells was reduced, further suggesting oxidative phosphorylation as a mediator of metastasis, a possible indicator of cells beginning metastasis, and a potential drug target.
Disclosure: The study authors reported no conflicts of interest.