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RETRACTED ARTICLE: Decreased Warburg effect induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic cancer

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This article was retracted on 22 September 2015

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.

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Acknowledgments

This research is supported by Health Bureau of Nanjing, China (Grant No. ZKX12040).

Conflict of interest

The authors declare that there is no conflict of interests.

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    Authors and Affiliations

    1. Department of Anorectal Surgery, Nanjing Municipal Hospital of T.C.M, 1#, Jinling Road, Nanjing, 210001, People’s Republic of China

      Haifeng Zong, Yang Zhang, Tiantian Cai & Yehuang Wang

    2. Zhangjiagang Wandong Anorectal Hospital, Zhangjiagang, 215600, People’s Republic of China

      Yong You

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    1. Haifeng Zong
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    2. Yang Zhang
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    Corresponding author

    Correspondence to Yehuang Wang.

    Additional information

    Haifeng Zong and Yang Zhang have contributed equally to this work.

    "This article has been retracted by the authors as it was discovered that duplication of several key experiments described herein were not possible because: The difference between acidification of culture medium in si-Ctrl group and si-ACLY could not be observed and the results of lactate production and glucose consumption could not be repeated. The authors regret any confusion caused."

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    Zong, H., Zhang, Y., You, Y. et al. RETRACTED ARTICLE: Decreased Warburg effect induced by ATP citrate lyase suppression inhibits tumor growth in pancreatic cancer. Med Oncol 32, 85 (2015). https://doi.org/10.1007/s12032-015-0540-z

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    • DOI: https://doi.org/10.1007/s12032-015-0540-z

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