|ZFIN ID: ZDB-PUB-160608-6|
The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development
Kuang, X., Liu, C., Fang, J., Ma, W., Zhang, J., Cui, S.
|Source:||FEBS letters 590(14): 2076-85 (Journal)|
|Registered Authors:||Kuang, Xia, Liu, Chao, Ma, Weirui, Zhang, Jian|
|Keywords:||Lkb1, early development, gluconeogenesis, glycolysis, zebrafish|
|PubMed:||27264935 Full text @ FEBS Lett.|
Kuang, X., Liu, C., Fang, J., Ma, W., Zhang, J., Cui, S. (2016) The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development. FEBS letters. 590(14):2076-85.
ABSTRACTThe liver kinase B1 (LKB1) is encoded by tumor suppressor gene STK11, which is mutated in Peutz-Jeghers Syndrome patients. Lkb1 plays indispensable roles in energy homeostasis. However, how Lkb1 regulates energy homeostasis in vivo remains to be fully understood. We found that inactivation of zebrafish Lkb1 upregulates pyruvate dehydrogenase kinase 2 expression and inactivates pyruvate dehydrogenase complex by increasing phosphorylation of pyruvate dehydrogenase. As a result, glycolysis is significantly enhanced as indicated by increased lactate production, which resembles the Warburg effect in cancer cells. Inhibition of Pdk2 in lkb1 mutants with Dichloroacetate, a promising anti-cancer drug, rescued the lactate production to wild-type level, suggesting the lkb1 mutant may be used to screen compounds targeting aerobic glycolysis in cancer therapy. This article is protected by copyright. All rights reserved.