6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro

Date

2017-01-31

Authors

Chesney, Jason A.

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Transforming growth factor [31 (TGF beta 1) 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 TGF beta 1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGF beta l '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 TGF beta 1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGF beta l -mediated increase in the invasive ability of the Panc1 cell cline a well -established model of TGF beta 1 -initiated EMT. Herein we demonstrate that TGF beta 1 induces PFKFB3 expression and stimulates glycolysis in Panci cells. We also show that s1RNA silencing of PFKFB3 prevents the stimulation of glycolysis and in vitro invasive ability of Panci cells by TGF beta 1. Furthermore, PFKFB3 silencing suppresses the TGFfil -mediated induction of the Snail protein, suggesting that PFKFB3 is required for the regulation of Snail expression by TGFfil. Taken together, our study identifies PFKFB3 as a key TGF beta 1 effector protein that mediates TGF beta 1's effect on Snail expression, invasion, and glycolysis.

Description

Keywords

Biochemistry & molecular biology, Biophysics, Glycolysis, PFKFB3, Snail, Transforming growth factor β1, Epithelial-mesenchymal transition, Factor-beta, Tgf-beta, Tumor-growth, Glucose-metabolism, Lactate production, Cancer, Pfkfb3, Snail, Inhibition

Citation

Yalçın, A. vd. (2017). ''6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro''. Biochemical and Biophysical Research Communications, 484(3), 687-693.