HMGCR is up-regulated in gastric cancer and promotes the growth and migration of the cancer cells

Gene. 2016 Aug 1;587(1):42-7. doi: 10.1016/j.gene.2016.04.029. Epub 2016 Apr 13.

Abstract

Alteration of metabolic profile is one of the hallmarks of cancer cells. Statin, the inhibitors for synthesis of cholesterol, has shown anti-cancer effects on the gastric cancer cells. However, the functions of its target, HMGCR, in the progression of gastric cancer remain unknown. In the present study, we investigated the expression profile and the biological functions of HMGCR in gastric cancer. It was found that the expression of HMGCR was increased in gastric cancer tissues. Over-expression of HMGCR promoted the growth and migration of gastric cancer cells, while knocking down the expression of HMGCR inhibited the growth, migration and tumorigenesis of gastric cancer cells. In the further molecular mechanism study, HMGCR was shown to activate Hedgehog/Gli1 signaling and promoted the expression of Gli1 target genes. Taken together, this study demonstrated the tumor-promoting effects of HMGCR in gastric cancer and suggested HMGCR as a promising therapeutic target.

Keywords: Cell growth and migration; Gastric cancer; HMGCR; Hedgehog/Gli1 signaling.

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Hedgehog Proteins / metabolism
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Mice
  • Mice, Nude
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Transcriptome
  • Up-Regulation

Substances

  • Hedgehog Proteins
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases