Date of Completion


Embargo Period



Breast cancer; epithelial-mesenchymal transition; metabolic reprogramming; aerobic glycolysis; Warburg effect

Major Advisor

Dr. Bruce A. White

Associate Advisor

Dr. Gordon G. Carmichael

Associate Advisor

Dr. John R. Harrison

Associate Advisor

Dr. Lisa M. Mehlmann

Field of Study

Biomedical Science


Doctor of Philosophy

Open Access

Campus Access


Metastasis is the leading cause of cancer related deaths and yet there are no targeted therapies for metastatic cancers. Epithelial-mesenchymal transition (EMT) promotes metastasis by inducing invasive properties in epithelial tumors. Although EMT-mediated cellular and molecular changes are well understood, very little is known about EMT-induced metabolic changes. To determine whether EMT induces metabolic alterations, 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, pentosephosphate pathway, hexosamine biosynthetic pathway, serine biosynthetic pathway, de novolipogenesis pathway and gluconeogenesis. Both EMT-derived breast cancer cells displayed enhanced aerobic glycolysis along with overexpression of specific glucose transporters (GLUT3, GLUT12), lactate dehydrogenase isoforms (LDHA, LDHB), monocarboxylate transporters (MCT2, MCT4) and the glycogen phosphorylase isoform, PYGL. In contrast, both EMT-derived breast cancer cells suppressed the expression of crucial enzymes in oxidative pentosephosphate pathway, serine biosynthetic pathway, de novo lipogenesis and gluconeogenesis. STAT3, a transcription factor involved in tumor initiation and progression, plays a role in the EMT-related changes in the expression of several specific enzymes and transporters. Both EMT-derived breast cancer cells show loss of the expression of miR-200 family, a group of microRNAs that inhibits EMT and promotes epithelial differentiation. miR-200c, a member of miR-200 family, suppresses the expression of PSAT1, a serine biosynthetic pathway enzyme, and ACC1, a de novo lipogenesis enzyme, in parental epithelial breast cancer cell lines. Both EMT-derived breast cancer cells express PSAT1 and ACC1 due to the loss of miR-200c. These miR-200c-induced changes may alter the acetylation status of specific nuclear and non-nuclear proteins. This study provides a broad overview of similar metabolic changes induced by EMT in two independent and substantially different epithelial breast cancer cell lines. These metabolic changes may be exploited to develop novel drugs to specifically target metastatic breast cancer cells.