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.
Date: 2016
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
MeSH Terms:
  • Animals
  • Glucose/genetics
  • Glucose/metabolism*
  • Glycolysis/physiology*
  • Protein-Serine-Threonine Kinases/biosynthesis
  • Protein-Serine-Threonine Kinases/genetics
  • Protein-Serine-Threonine Kinases/metabolism*
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Up-Regulation/physiology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 27264935 Full text @ FEBS Lett.
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ABSTRACT
The 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.
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