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

Abstract

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 human breast adenocarcinoma MDA-MB-231 line, alteration in growth and energy metabolisms associated with enhanced metastatic potential were described. Glycolysis and oxidative phosphorylation (OXPHOS) was characterized 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 relevant metabolic regulators. Heightened mitochondrial respiration is potentially underpinned by increased expression 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 active. We also identified differentially expressed metabolic genes, such as IDH2, that may play a part in the metastatic process beyond energy reprogramming.

Keywords

Breast cancer / energy reprogramming / cancer metabolism / metastasis / RNA-seq

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