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.
Department of Cell Biology, University of Connecticut Heath Center, Farmington, CT 06030, USA.
Yuvabharath
Y
Kondaveeti
Department of Biology, University of St. Joseph, West Hartford, CT 06117, USA.
Irene K
IK
Guttilla Reed
Department of Cell Biology, University of Connecticut Heath Center, Farmington, CT 06030, USA. Electronic address: bwhite@uchc.edu.
Bruce A
BA
White
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005943:Gluconeogenesis; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism
D007773:Lactates; D007770:L-Lactate Dehydrogenase; D024981:Glycogen Phosphorylase
Aerobic glycolysis; Breast cancer; Epithelial–mesenchymal transition; Metabolic reprogramming; Warburg effect