Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis

Int J Biol Sci. 2021 Apr 23;17(7):1782-1794. doi: 10.7150/ijbs.59068. eCollection 2021.

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: Aldolase A; Enzymatic Activity; Glycolysis.; Intrahepatic Cholangiocarcinoma; Metabolism Reprogram.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms / enzymology
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cholangiocarcinoma / enzymology
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology
  • Fructose-Bisphosphate Aldolase / biosynthesis
  • Fructose-Bisphosphate Aldolase / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Glycolysis / genetics*
  • Humans
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Signal Transduction

Substances

  • RNA, Neoplasm
  • Fructose-Bisphosphate Aldolase