Up-regulated ANP32E promotes the thyroid carcinoma cell proliferation and migration via activating AKT/mTOR/HK2-mediated glycolysis

Gene. 2020 Aug 5;750:144681. doi: 10.1016/j.gene.2020.144681. Epub 2020 Apr 15.

Abstract

Thyroid cancer (THCA) is one of the most common endocrine tumors and keeps rapidly increasing worldwide. Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a H2A.Z histone chaperone that regulates the expression of various genes. It has been shown that ANP32E promotes breast cancer development, whereas its role in THCA remains unknown. In this study, we found that ANP32E was significantly overexpressed in THCA tissues. Down-regulation of ANP32E inhibited the growth, cell cycle progression, DNA synthesis, glycolysis, migration and increased apoptosis in K1 and TPC-1 cells. Opposite results were observed in ANP32E-overexpressing THCA cells. At the molecular level, ANP32E up-regulated MMP9 and MMP13, and activated AKT/mTOR/HK2 signaling in THCA cells. Positive correlation between ANP32E and HK2 was found in THCA tissues. Importantly, silencing of HK2 repressed glycolysis. Inhibition of AKT/mTOR reduced cell proliferation, cell cycle progression and migration in THCA cells. Our findings suggest that ANP32E promotes THCA cell proliferation and migration via potentiating AKT/mTOR/HK2-mediated glycolysis.

Keywords: AKT/mTOR/HK2; ANP32E; Glycolysis; Thyroid carcinoma.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Female
  • Glycolysis
  • Hexokinase / metabolism
  • Humans
  • Male
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism*
  • Nuclear Proteins / genetics
  • Nucleosomes / genetics
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Transcriptional Activation

Substances

  • ANP32E protein, human
  • Molecular Chaperones
  • Nuclear Proteins
  • Nucleosomes
  • HK2 protein, human
  • Hexokinase
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt