Published online Nov 21, 2018. doi: 10.3748/wjg.v24.i43.4893
Peer-review started: July 9, 2018
First decision: August 31, 2018
Revised: September 27, 2018
Accepted: October 15, 2018
Article in press: October 15, 2018
Published online: November 21, 2018
Pancreatic cancer is a highly lethal disease that is characterized by metastasis. Uncovering novel functions of metastasis regulators might provide novel predictive and treatment targets.
Aerobic glycolysis has been implicated in multiple processes of cancer progression. However, the impact of the cancer metastasis gene zinc finger E-box-binding homeobox 1 (ZEB1) on aerobic glycolysis has seldom been discussed, and the molecular link is lacking.
To uncover the roles of ZEB1 in aerobic glycolysis regulation and establish the molecular mechanism.
ZEB1 was silenced in pancreatic cancer cells to examine its impact on aerobic glycolysis. The impact of ZEB1 on mitochondrion-localized tumor suppressors sirtuin 3 (SIRT3), 4 and 5 was assessed by real-time polymerase chain reaction and western blotting. The transcriptional regulation of ZEB1 on SIRT3 expression was assayed by dual-luciferase and chromatin immunoprecipitation assays. The underlying molecular mechanism that governs the effect of ZEB1 on SIRT3 expression was confirmed by protein interaction, promoter luciferase and chromatin immunoprecipitation assays.
ZEB1 positively regulated aerobic glycolysis. Mechanistically, ZEB1 regulated aerobic glycolysis by suppression of SIRT3 via interaction with methyl-CpG binding domain protein 1.
The metastasis gene ZEB1 is an important regulator of aerobic glycolysis.
The impact of ZEB1 and SIRT3 on the prediction of prognosis and the prospect for targeting metastasis by regulation of glycolysis should be investigated in the future.