Akt mediates TIGAR induction in HeLa cells following PFKFB3 inhibition

Neoplastic cells metabolize higher amounts of glucose relative to normal cells in order to cover increased energetic and anabolicneeds. Inhibition of the glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) diminishes cancer cell proliferation and tumour growth in animals. In this work, we investigate the crosstalk between PFKFB3 and TIGAR ( TP53-Induced Glycolysisand Apoptosis Regulator), a protein known to protect cells from oxidative stress. Our results show consistent TIGAR induction in HeLa cells in response to PFKFB3 knockdown. Upon PFKFB3 silencing, cells undergo oxidative stressand trigger Akt phosphorylation. This leads to induction of a TIGAR-mediated pro-survival pathway that reduces both oxidative stressand cell death. As TIGAR is known to have a role in DNA repair, it could serve as a potential target for the development of effective antineoplastic therapies. This article is protected by copyright. All rights reserved.