Int J Biol Sci 2021; 17(7):1782-1794. doi:10.7150/ijbs.59068

Research Paper

Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis

Xiang Li1,2*, Chang Yu2*, Yichun Luo2*, Jiacheng Lin2, Fang Wang2, Xuehua Sun2, Yueqiu Gao2, Weifeng Tan1✉, Qiang Xia1✉, Xiaoni Kong2✉

1. Department of Hepatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
2. Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
* These authors contributed equally to this work.

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Citation:
Li X, Yu C, Luo Y, Lin J, Wang F, Sun X, Gao Y, Tan W, Xia Q, Kong X. Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis. Int J Biol Sci 2021; 17(7):1782-1794. doi:10.7150/ijbs.59068. Available from https://www.ijbs.com/v17p1782.htm

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Abstract

Energy metabolism reprogramming has been implicated in tumorigenesis and development. Key metabolism enzyme Aldolase A (ALDOA) has been shown to be highly expressed and involved in various kinds of cancers including hepatocellular carcinoma. In this study, we found that ALDOA was highly expressed in clinical intrahepatic cholangiocarcinoma (ICC) tissues, and its high expression was negatively correlated with overall survival (OS) and recurrence-free survival (RFS) in ICC patients. Knockdown of ALDOA expression significantly inhibited the proliferation and migration of ICC both in vitro and in vivo, while highly-expressed ALDOA in ICC cells promoted the proliferation and migration of ICC cells. By applying ALDOA inhibitor and metabolic mass spectrometry tests, we demonstrated that ALDOA modulated the biological characteristics and metabolic level of ICC cells depending on its enzymatic activity. In summary, ALDOA promotes ICC proliferation and migration by enhancing ICC cells glycolysis. Blocking enzymatic activity of ALDOA provides a strategy to inhibit ICC.

Keywords: Intrahepatic Cholangiocarcinoma, Aldolase A, Metabolism Reprogram, Enzymatic Activity, Glycolysis.