研究领域

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We are focused on metabolic reprogramming that accompanies epithelial-mesenchymal transition (EMT) in human breast cancer cell lines. We used 3-dimensional mammosphere culture conditions to induce a stable EMT in the two epithelial MCF7 and BT474 breast cancer cell lines, thereby generating corresponding post-EMT mesenchymal cell lines, termed MCF7M and BT474M cells. We are currently utilizing a 3-dimensional culture system in Matrigel, along with physiological levels of glucose, lactate, glutamine and pyruvate, in order to more accurately mimic the in vivo condition. We recently reported that both epithelial cell lines are more oxidative, and express enzymes involved in reverse glycolysis that potentially redirect carbons to anabolic pathways involved in cell growth. In contrast, the two mesenchymal cell lines proliferate faster and are more motile. The MCF7M and BT474M cells are also significantly more glycolytic, expressing higher levels of GLUT transporters and consuming more glucose, and expressing higher levels of the lactate transporter, MCT4, and producing more lactate than the epithelial cells. We are currently examining how lactate metabolism is shifted in these cell lines, and the potential role of the endogenous lactate transporter, GPR81, in the regulation of lactate metabolism. Most recently, we have also examined how the NAD+/NADH ratio might be altered by but also control metabolic reprogramming in the epithelial vs mesenchymal cell lines. In this context, we have begun to examine whether the metabolism of ethanol, which is linked to a higher risk for diagnosis of some forms of breast cancer, might impact the NAD+/NADH ratio and thus metabolic reprogramming, cell proliferation and cell viability.