Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis

Trends Cancer. 2023 Jun;9(6):480-489. doi: 10.1016/j.trecan.2023.03.003. Epub 2023 Apr 5.

Abstract

Cancer progression is a highly balanced process and is maintained by a sequence of finely tuned metabolic pathways. Stearoyl coenzyme A desaturase-1 (SCD1), the fatty enzyme that converts saturated fatty acids into monounsaturated fatty acids, is a critical modulator of the fatty acid metabolic pathway. SCD1 expression is associated with poor prognosis in several cancer types. SCD1 triggers an iron-dependent cell death called ferroptosis and elevated levels of SCD1 protect cancer cells against ferroptosis. Pharmacological inhibition of SCD1 as monotherapy and in combination with chemotherapeutic agents shows promising antitumor potential in preclinical models. In this review, we summarize the role of SCD in cancer cell progression, survival, and ferroptosis and discuss potential strategies to exploit SCD1 inhibition in future clinical trials.

Keywords: NSCLC; SCD1; cancer therapy; fatty acid metabolism; ferroptosis; immunotherapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Coenzyme A
  • Fatty Acid Desaturases
  • Fatty Acids / metabolism
  • Ferroptosis*
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Stearoyl-CoA Desaturase / metabolism

Substances

  • Fatty Acids
  • Fatty Acid Desaturases
  • Coenzyme A
  • Stearoyl-CoA Desaturase