GRM4 inhibits the proliferation, migration, and invasion of human osteosarcoma cells through interaction with CBX4

Biosci Biotechnol Biochem. 2020 Feb;84(2):279-289. doi: 10.1080/09168451.2019.1673147. Epub 2019 Oct 4.

Abstract

In recent years, the survey of metabolic glutamate receptor 4 (GRM4) in tumor biology has been gradually concerned. There are currently few studies on GRM4 in osteosarcoma, and the biological function is not clear. Analysis of TCGA database showed that there was no substantial deviation in the expression of GRM4 between osteosarcoma and normal tissues. In the subsequent experiments, there is no significant difference in either mRNA or protein levels among immortalized human osteoblasts and various osteosarcoma cells. With the overexpression of GRM4, cell proliferation, migration and invasion were inhibited obviously. It was further revealed that GRM4 can interact with CBX4 to restrict the nuclear localization of CBX4 and affect the transcriptional activity of HIF-1α. This is the evidence supporting the interaction between GRM4 and CBX4, which could inhibit the malignant behavior of osteosarcoma cells through the GRM4/CBX4/HIF-1α signaling pathway.

Keywords: CBX4; GRM4; HIF-1α; Osteosarcoma.

MeSH terms

  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ligases / metabolism*
  • Neoplasm Invasiveness / prevention & control*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Polycomb-Group Proteins / metabolism*
  • Protein Binding
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, Metabotropic Glutamate / physiology*
  • Signal Transduction
  • Transcription, Genetic

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Polycomb-Group Proteins
  • Receptors, Metabotropic Glutamate
  • Ligases
  • CBX4 protein, human
  • metabotropic glutamate receptor 4