Squalene epoxidase as a promising metabolic target in cancer treatment

Cancer Lett. 2018 Jul 1:425:13-20. doi: 10.1016/j.canlet.2018.03.034. Epub 2018 Mar 27.

Abstract

Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. In the present review, we focus on squalene epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis, retracing its history since its discovery as an antimycotic target to its description as an emerging metabolic oncogene by amplification with clinical relevance in cancer. We review the published literature assessing the association between SE over-expression and poor prognosis in this disease. We assess the works demonstrating how SE promotes tumor cell proliferation and migration, and displaying evidence of cancer cell demise in presence of human SE inhibitors in in vitro and in vivo models. Taken together, robust scientific evidence has by now accumulated pointing out SE as a promising novel therapeutic target in cancer treatment.

Keywords: Cancer treatment; Cell proliferation and migration; Cholesterol synthesis; Metabolism; Squalene epoxidase.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Disease Progression
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Signal Transduction / drug effects
  • Squalene Monooxygenase / antagonists & inhibitors
  • Squalene Monooxygenase / genetics*
  • Squalene Monooxygenase / metabolism*
  • Up-Regulation* / drug effects

Substances

  • Enzyme Inhibitors
  • Squalene Monooxygenase