Akt mediates TIGAR induction in HeLa cells following PFKFB3 inhibition.

Abstract:

:Neoplastic cells metabolize higher amounts of glucose relative to normal cells in order to cover increased energetic and anabolic needs. 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 Glycolysis and 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 stress and trigger Akt phosphorylation. This leads to induction of a TIGAR-mediated prosurvival pathway that reduces both oxidative stress and 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Simon-Molas H,Calvo-Vidal MN,Castaño E,Rodríguez-García A,Navarro-Sabaté À,Bartrons R,Manzano A

doi

10.1002/1873-3468.12338

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

2915-26

issue

17

eissn

0014-5793

issn

1873-3468

journal_volume

590

pub_type

信件
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