Transforming growth factor β1 upregulates 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-4 expression in A549 and MCF-10A cells.

Autor: Altunok TH; Department of Biochemistry, School of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey., Muchut RJ; Department of Molecular Enzymology, Coastal Agrobiotechnology Institute, National University of Litoral, Santa Fe, Argentina., Iglesias AA; Department of Molecular Enzymology, Coastal Agrobiotechnology Institute, National University of Litoral, Santa Fe, Argentina., Yalcin A; Department of Biochemistry, School of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey.
Jazyk: angličtina
Zdroj: Cell biochemistry and function [Cell Biochem Funct] 2023 Dec; Vol. 41 (8), pp. 1220-1229. Date of Electronic Publication: 2023 Sep 14.
DOI: 10.1002/cbf.3856
Abstrakt: Transforming growth factor β1 (TGFβ1) induces a cellular process known as epithelial-mesenchymal transition (EMT) associated with metabolic reprogramming, including enhanced glycolysis. Given the involvement of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFKFB) enzymes in glycolysis, we aimed to investigate whether TGFβ1 regulates expressions of PFKFB genes and if PFKFBs are required for TGFβ1-driven phenotypes. A549 and MCF-10A cell lines were used as TGFβ1-driven EMT models. Messenger RNA expressions of PFKFB and EMT genes were determined by real-time quantitative polymerase chain reaction. A small interfering RNA approach was used to deplete PFKFB4 expression. A Matrigel invasion assay was conducted to assess the effect of PFKFB4 silencing on the TGFβ1-enhanced invasion of A549 cells. F2,6BP levels were analyzed using an enzyme-coupled assay. Glucose and lactate concentrations were determined using colorimetric assays. TGFβ1 robustly induced expression of the fourth isoform of PFKFBs, PFKFB4, in both cell lines. PFKFB4 depletion partially inhibits mesenchymal transdifferentiation caused by TGFβ1 in A549 cells, as assessed by microscopy. Inductions of Snail in MCF-10A cells and Fibronectin in A549 cells and repressions of E-cadherin in both cell lines by TGFβ1 are attenuated by PFKFB4 silencing. PFKFB4 silencing reduces F2,6BP and glycolytic activity, although TGFβ1 alone does not affect these parameters. Finally, PFKFB4 depletion suppresses the TGFβ1-driven invasion of A549 cells through Matrigel. Presented data suggest that TGFβ1 induces the expression of PFKFB4 in A549 and MCF-10 cells, and PFKFB4 may be required for TGFβ1-driven phenotypes such as EMT and invasion in these models.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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