The role of OXCT1 in the pathogenesis of cancer as a rate-limiting enzyme of ketone body metabolism

Life Sci. 2017 Aug 15:183:110-115. doi: 10.1016/j.lfs.2017.07.003. Epub 2017 Jul 4.

Abstract

Cancer cells are well documented to reprogram their metabolism in order to support the maintenance and reproduction. 3-oxoacid CoA-transferase 1 (OXCT1) is a key enzyme in ketone body metabolism that catalyzes the first and rate-determining step of ketolysis. The product of OXCT1 converts to acetyl-CoA and finally fed into the tricarboxylic acid cycle for oxidation and ATP production. However, little is known of its regulation right now. Recently, some studies suggested that OXCT1 participates in tumorigenesis and signaling in cancer cells. Furthermore, our recent work showed that a marked elevation of OXCT1 expression in different categories of cancer cells. Here we review the metabolic functions of OXCT1 and its surprising roles in supporting the biological hallmarks of malignancy. We also review recent efforts in exploring the mechanism responsible for the tumor promoting effect of OXCT1 and suggest a novel therapeutic target for cancer therapy.

Keywords: Cancer; Ketone body; OXCT1; Pathogenesis.

Publication types

  • Review

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Adenosine Triphosphate / metabolism
  • Animals
  • Coenzyme A-Transferases / genetics
  • Coenzyme A-Transferases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ketones / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Signal Transduction

Substances

  • Ketones
  • Acetyl Coenzyme A
  • Adenosine Triphosphate
  • Coenzyme A-Transferases
  • 3-ketoacid CoA-transferase