TY  - JOUR
A1  - Bernacchioni, Caterina
A1  - Ghini, Veronica
A1  - Cencetti, Francesca
A1  - Japtok, Lukasz
A1  - Donati, Chiara
A1  - Bruni, Paola
A1  - Turano, Paola
T1  - NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells
JF  - Molecular oncology / Federation of European Biochemical Societies
N2  - Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR- based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.
KW  - NMR-based metabolomics
KW  - ovarian cancer
KW  - sphingosine kinase-1
KW  - Warburg effect
Y1  - 2017
U6  - https://doi.org/10.1002/1878-0261.12048
SN  - 1878-0261
VL  - 11
SP  - 517
EP  - 533
PB  - Wiley
CY  - Hoboken
ER  -