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Updated: Jan 6, 2026
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
GRM4 inhibits the proliferation, migration, and invasion of human osteosarcoma cells through interaction with CBX4
Zengliang Zhang1,2, Nan Li1, Xing Wei3
1Department of orthopaedics, Fourth Medical Center of PLA General Hospital, Beijing, China.
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.
Insights
Metabolic glutamate receptor 4 (GRM4) overexpression inhibits osteosarcoma cell growth and invasion. GRM4 interacts with CBX4, impacting HIF-1α activity and suppressing tumor malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Metabolic glutamate receptor 4 (GRM4) is increasingly studied in tumor biology.
- Limited research exists on GRM4's role in osteosarcoma, with its function unclear.
- Initial analysis shows no significant GRM4 expression difference between osteosarcoma and normal tissues.
Purpose of the Study:
- To investigate the biological function of GRM4 in osteosarcoma.
- To elucidate the molecular mechanism underlying GRM4's effect on osteosarcoma progression.
Main Methods:
- TCGA database analysis for GRM4 expression.
- mRNA and protein level analysis in osteoblasts and osteosarcoma cells.
- Overexpression studies of GRM4 in osteosarcoma cells.
- Co-immunoprecipitation to assess protein interactions.
- Western blotting and qPCR to analyze protein and gene expression.
Main Results:
- GRM4 expression showed no significant difference in osteosarcoma versus normal tissues or cell lines.
- Overexpression of GRM4 significantly inhibited osteosarcoma cell proliferation, migration, and invasion.
- GRM4 was found to interact with CBX4, restricting its nuclear localization.
- This interaction affected the transcriptional activity of HIF-1α.
Conclusions:
- GRM4 plays an inhibitory role in osteosarcoma malignancy.
- The GRM4/CBX4/HIF-1α signaling pathway is a key regulator of osteosarcoma cell behavior.
- GRM4's interaction with CBX4 suppresses tumor progression by modulating HIF-1α activity.
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