Altered energy metabolism and metabolic gene expression associated with increased metastatic capacity identified in MDA-MB-231 cell line variants

摘要

Aim: Despite current advances in therapies and the gradual decline in breast cancer-related mortality, metastasis remains a major therapeutic challenge for treatment. Energy reprogramming is now recognized to be an important part of tumorigenic processes, but its relevance in metastatic dissemination has yet to be elucidated. Methods: Using the MDA-MB-231HM.LNm5 cell line, a novel, highly metastatic variant line derived from TN hu-man breast adenocarcinoma MDA-MB-231 line, alteration in growth and energy metabolisms associated with en-hanced metastatic potential were described. Glycolysis and oxidative phosphorylation (OXPHOS) was character-ized using the seahorse XF analyzer. Whole transcriptome sequencing (RNA-seq) and quantitative real-time PCR was used to ascertain expression differences in metabolic genes. Results: We observed reduced proliferation, and an elevation of both glycolytic and OXPHOS metabolism in the highly metastatic daughter line. The elevated metabolic rate is only partially reflected by transcript levels of rel-evant metabolic regulators. Heightened mitochondrial respiration is potentially underpinned by increased expres-sion mitochondrial electron transport chain components. However, increased glycolysis was not underpinned by up-regulation of metabolic genes encoding enzymes participating in glycolysis. Conclusion: Our results indicate breast tumour cells with elevated metastatic propensity are more metabolic ac-tive. We also identified differentially expressed metabolic genes, such as IDH2, that may play a part in the meta-static process beyond energy reprogramming.