Published in:
01-03-2015 | Original Paper
RETRACTED ARTICLE: Decreased Warburg effect
induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic
cancer
Authors:
Haifeng Zong, Yang Zhang, Yong You, Tiantian Cai, Yehuang Wang
Published in:
Medical Oncology
|
Issue 3/2015
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Abstract
ATP citrate lyase (ACLY) is responsible for the conversion of cytosolic citrate
into acetyl-CoA and oxaloacetate, and the first rate-limiting enzyme involved in de
novo lipogenesis. Recent studies have demonstrated that inhibition of elevated ACLY
results in growth arrest and apoptosis in a subset of cancers; however, the
expression pattern and underlying biological function of ACLY in pancreatic ductal
adenocarcinoma (PDAC) remains unclear. In the current study, overexpressed ACLY was
more commonly observed in PDAC compared to normal pancreatic tissues. Kaplan–Meier
survival analysis showed that high expression level of ACLY resulted in a poor
prognosis of PDAC patients. Silencing of endogenous ACLY expression by siRNA in
PANC-1 cells led to reduced cell viability and increased cell apoptosis.
Furthermore, significant decrease in glucose uptake and lactate production was
observed after ACLY was knocked down, and this effect was blocked by
2-deoxy-d-glucose, indicating that ACLY
functions in the Warburg effect affect PDAC cell growth. Collectively, this study
reveals that suppression of ACLY plays an anti-tumor role through decreased Warburg
effect, and ACLY-related inhibitors might be potential therapeutic approaches for
PDAC.