6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor β1-enhanced invasion of Panc1 cells in vitro.
Transforming growth factor β1 (TGFβ1) 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 TGFβ1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGFβ1'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 TGFβ1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGFβ1-mediated increase in the invasive ability of the Panc1 cell cline-a well-established model of TGFβ1-initiated EMT. Herein we demonstrate that TGFβ1 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 TGFβ1. Furthermore, PFKFB3 silencing suppresses the TGFβ1-mediated induction of the Snail protein, suggesting that PFKFB3 is required for the regulation of Snail expression by TGFβ1. Taken together, our study identifies PFKFB3 as a key TGFβ1 effector protein that mediates TGFβ1's effect on Snail expression, invasion, and glycolysis.
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey. Electronic address: ayalcin@uludag.edu.tr.
Abdullah
A
Yalcin
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Tugba H
TH
Solakoglu
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Selahattin C
SC
Ozcan
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Saime
S
Guzel
Department of Histology & Embryology, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Sabire
S
Peker
Department of General Biology, Division of Biology, School of Arts & Science, Uludag University, Bursa, 16059, Turkey.
Serap
S
Celikler
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Basak D
BD
Balaban
Department of General Biology, Division of Biology, School of Arts & Science, Uludag University, Bursa, 16059, Turkey.
Elif
E
Sevinc
Department of Biochemistry, School of Veterinary Medicine, Uludag University, Bursa, 16059, Turkey.
Yunus
Y
Gurpinar
J. G. Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA. Electronic address: jason.chesney@louisville.edu.
Jason A
JA
Chesney
D045744:Cell Line, Tumor; D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D010446:Peptide Fragments; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; C464671:transforming growth factor beta1 (41-65); C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2; D005947:Glucose
Glycolysis; PFKFB3; Snail; Transforming growth factor β1