Open AccessNMR metabolomics highlights sphingosine kinase‐1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells
Author(s) -
Bernacchioni Caterina,
Ghini Veronica,
Cencetti Francesca,
Japtok Lukasz,
Donati Chiara,
Bruni Paola,
Turano Paola
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12048
Subject(s) - warburg effect , anaerobic glycolysis , glycolysis , citric acid cycle , metabolomics , sphingosine , carcinogenesis , biology , downregulation and upregulation , cancer cell , metabolic pathway , lactate dehydrogenase a , microbiology and biotechnology , sphingosine kinase 1 , oxidative phosphorylation , biochemistry , cancer research , chemistry , sphingosine 1 phosphate , cancer , metabolism , bioinformatics , genetics , receptor , gene
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 CO 2 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.