RESUMO
Transforming growth factor ß1 (TGFß1) is a well-established inducer of the epithelial-mesenchymal transition (EMT) that is essential for the acquisition of malignant properties, such as invasion, in tumor cells. Although recent studies suggest that the EMT in tumor cells is associated with reprogramming of energy metabolism and TGFß1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGFß1's effect on glycolysis and glycolytic regulators in transformed cells. Given the known regulatory role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 (PFKFB3) in glycolysis and association of glycolytic activity with malignant features such as invasion, we sought to investigate whether TGFß1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGFß1-mediated increase in the invasive ability of the Panc1 cell cline-a well-established model of TGFß1-initiated EMT. Herein we demonstrate that TGFß1 induces PFKFB3 expression and stimulates glycolysis in Panc1 cells. We also show that siRNA silencing of PFKFB3 prevents the stimulation of glycolysis and in vitro invasive ability of Panc1 cells by TGFß1. Furthermore, PFKFB3 silencing suppresses the TGFß1-mediated induction of the Snail protein, suggesting that PFKFB3 is required for the regulation of Snail expression by TGFß1. Taken together, our study identifies PFKFB3 as a key TGFß1 effector protein that mediates TGFß1's effect on Snail expression, invasion, and glycolysis.