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

• Metabolic reprogramming induced by epithelial–mesenchymal transition (EMT) was assessed.
• EMT enhanced aerobic glycolysis and glycolytic dependency.
• EMT-derived breast cancer cells displayed overexpression of certain enzymes and transporters related to glycolysis.
• EMT-derived breast cancer cells showed loss of key enzymes in specific anabolic side pathways and gluconeogenesis.
• STAT3 signaling is required for certain metabolic alterations observed in EMT-derived breast cancer cells.

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-474EMT and MCF-7EMT) 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.