A key role for transketolase-like 1 in tumor metabolic reprogramming

作者：Diaz Moralli Santiago; Aguilar Esther; Marin Silvia; Coy Johannes F; Dewerchin Mieke; Antoniewicz Maciek R; Meca Cortes Oscar; Notebaert Leen; Ghesquiere Bart; Eelen Guy; Thomson Timothy M; Carmeliet Peter^*; Cascante Marta^*

来源：Oncotarget, 2016, 7(32): 51875-51897.

DOI：10.18632/oncotarget.10429

• tumor metabolism
• metabolic reprogramming
• transketolase-like 1
• lipid metabolism
• pentose phosphate pathway

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.

• 出版日期2016-8-9