A key role for transketolase-like 1 in tumor metabolic reprogramming
Metabolic reprogramming, a crucial cancer hallmark, shifts metabolic pathways such as glycolysis, tricarboxylic acid cycle or lipogenesis, to enable the growth characteristics of cancer cells. Here, we provide evidence that transketolase-like 1 (TKTL1) orchestrates aerobic glycolysis, fatty acid and nucleic acid synthesis, glutamine metabolism, protection against oxidative stress and cell proliferation. Furthermore, silencing of TKTL1 reduced the levels of sphingolipids such as lactosylceramide (a sphingolipid regulating cell survival, proliferation and angiogenesis) and phosphatidylinositol (which activates PI3K/Akt/mTOR signaling). Thus, in addition to its well-known roles in glucose and amino acid metabolism, TKTL1 also regulates lipid metabolism. In conclusion, our study provides unprecedented evidence that TKTL1 plays central roles in major metabolic processes subject to reprogramming in cancer cells and thus identifies TKTL1 as a promising target for new anti-cancer therapies. ; This work was supported by grants to M.C. (Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) – Generalitat de Catalunya, 2014SGR1017; ICREA Academia from the ICREA foundation; and MINECO-European Commission FEDER – Una manera de hacer Europa, SAF2014-56059-R), T.M.T. (MINECO-European Commission FEDER – Una manera de hacer Europa, SAF2015-66984-C2-1-R; and Xarxa de Referència en Biotecnologia) and P.C. (Research Foundation-Flanders (FWO), Belgian Science Policy grant (IUAP P7/03); long-term structural Methusalem funding by the Flemish Government; European Research Council (ERC) Advanced Research Grant (EU-ERC269073); and AXA Research Fund). ; Peer Reviewed