Silencing of Glut1 induces chemoresistance via modulation of Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells

Arch Biochem Biophys. 2017 Dec 15:636:110-122. doi: 10.1016/j.abb.2017.08.009. Epub 2017 Aug 10.

Abstract

Cancer cells require increased aerobic glycolysis to support rapid cell proliferation. For their increased energy demands, cancer cells express glucose transporter (Glut) proteins at a high level. Glut1 is associated with basal-like breast cancer and is considered a potential therapeutic target. To investigate the possibility of Glut1 as a therapeutic target in breast cancer cells, we downregulated Glut1 in triple-negative breast cancer (TNBC) cell lines using a short hairpin system. We determined whether Glut1 silencing might enhance anti-proliferative effect of chemotherapeutic agents. Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3β (Ser9)/β-catenin/survivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated.

Keywords: Chemoresistance; Glut1; Triple-negative breast cancer.

MeSH terms

  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Glucose Transporter Type 1 / biosynthesis*
  • Glucose Transporter Type 1 / genetics
  • Glycogen Synthase Kinase 3 beta / biosynthesis*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis*
  • Inhibitor of Apoptosis Proteins / genetics
  • Proto-Oncogene Proteins c-akt / biosynthesis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction*
  • Survivin
  • Up-Regulation*
  • beta Catenin / biosynthesis*
  • beta Catenin / genetics

Substances

  • BIRC5 protein, human
  • Glucose Transporter Type 1
  • Inhibitor of Apoptosis Proteins
  • SLC2A1 protein, human
  • Survivin
  • beta Catenin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt