Epithelial-mesenchymal transition induces similar metabolic alterations in two independent breast cancer cell lines.

Epithelial-mesenchymal transition (EMT) induces invasive properties in epithelial tumors and promotes metastasis. Although EMT-mediated cellular and molecular changes are well understood, very little is known about EMT-induced metabolic changes. HER2-positive BT-474 breast cancer cells were induced to undergo a stable EMT using mammosphere culture, as previously described by us for the ERα-positive MCF-7 breast cancer cells. Two epithelial breast cancer cell lines (BT-474 and MCF-7) were compared to their respective EMT-derived mesenchymal progeny (BT-474(EMT) and MCF-7(EMT)) for changes in metabolic pathways including glycolysis, glycogen metabolism, anabolic pathways and gluconeogenesis. Both EMT-derived cells displayed enhanced aerobic glycolysis along with the overexpression of specific glucose transporters, lactate dehydrogenase isoforms, monocarboxylate transporters and glycogen phosphorylase isoform. In contrast, both EMT-derived cells suppressed the expression of crucial enzymes in anabolic pathways and gluconeogenesis. STAT3, a transcription factor involved in tumor initiation and progression, plays a role in the EMT-related changes in the expression of specific enzymes and transporters. This study provides a broad overview of similar metabolic changes induced by EMT in two independent breast cancer cell lines. These metabolic changes may provide novel therapeutic targets for metastatic breast cancer.