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The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development
Author(s) -
Kuang Xia,
Liu Chao,
Fang Junshun,
Ma Weirui,
Zhang Jian,
Cui Sheng
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12237
Subject(s) - glycolysis , warburg effect , pyruvate dehydrogenase kinase , pyruvate dehydrogenase complex , zebrafish , pyruvate kinase , mutant , kinase , biology , pkm2 , lactate dehydrogenase a , energy homeostasis , anaerobic glycolysis , microbiology and biotechnology , homeostasis , chemistry , cancer research , biochemistry , gene , metabolism , enzyme , receptor
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 anticancer 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.