Stearoyl-CoA desaturase and tumorigenesis

Chem Biol Interact. 2020 Jan 25;316:108917. doi: 10.1016/j.cbi.2019.108917. Epub 2019 Dec 12.

Abstract

Stearoyl-CoA desaturase (SCD) generates monounsaturated fatty acids (MUFAs) which contribute to cell growth, survival, differentiation, metabolic regulation and signal transduction. Overexpression of SCD is evident and implicated in metabolic diseases such as diabetes and non-alcoholic fatty liver disease. SCD also stimulates canonical Wnt pathway and YAP activation in support of stemness and tumorigenesis. SCD facilitates metabolic reprogramming in cancer which is mediated, at least in part, by regulation of AKT, AMPK, and NF-kB via MUFAs. Our research has revealed the novel positive loop to amplify Wnt signaling through stabilization of LRP5/6 in both hepatic stellate cells and liver tumor-initiating stem cell-like cells. As such, this loop is pivotal in promoting liver fibrosis and liver tumor development. This review summarizes the mechanisms of SCD-mediated tumor promotion described by recent studies and discusses the future prospect for SCD-mediated signaling crosstalk as a potential therapeutic target for cancer.

Keywords: Hepatic stellate cells; Wnt; YAP; β-catenin.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis*
  • Cell Cycle Proteins / metabolism
  • Hepatic Stellate Cells / cytology
  • Hepatic Stellate Cells / metabolism
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism*
  • Wnt Signaling Pathway

Substances

  • Cell Cycle Proteins
  • Stearoyl-CoA Desaturase