Complementary ACSL isoforms contribute to a non-Warburg advantageous energetic status characterizing invasive colon cancer cells

Sci Rep. 2017 Sep 11;7(1):11143. doi: 10.1038/s41598-017-11612-3.

Abstract

Metabolic reprogramming is one of cancer hallmarks. Here, we focus on functional differences and individual contribution of acyl coA synthetases (ACSL) isoforms to the previously described ACSL/stearoyl-CoA desaturase (ACSL1/ACSL4/SCD) metabolic network causing invasion and poor prognosis in colorectal cancer (CRC). ACSL4 fuels proliferation and migration accompanied by a more glycolytic phenotype. Conversely, ACSL1 stimulates invasion displaying a lower basal respiratory rate. Acylcarnitines elevation, polyunsaturated fatty acids (PUFA) lower levels, and monounsaturated fatty acids (MUFA) upregulation characterize the individual overexpression of ACSL1, ACSL4 and SCD, respectively. However, the three enzymes simultaneous overexpression results in upregulated phospholipids and urea cycle derived metabolites. Thus, the metabolic effects caused by the network are far from being caused by the individual contributions of each enzyme. Furthermore, ACSL/SCD network produces more energetically efficient cells with lower basal respiration levels and upregulated creatine pathway. These features characterize other invasive CRC cells, thus, ACSL/SCD network exemplifies specific metabolic adaptations for invasive cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Coenzyme A Ligases / genetics*
  • Coenzyme A Ligases / metabolism
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Computational Biology / methods
  • Energy Metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes
  • Metabolic Networks and Pathways
  • Metabolome
  • Metabolomics

Substances

  • Isoenzymes
  • Coenzyme A Ligases