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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells
Gargi Sivaram1, Srijana Upadhyay2, Sarah Kakwan3
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Cancers
|June 26, 2026
Summary
DIM-3,5 compounds, dual NR4A1/NR4A2 ligands, inhibit MerTK expression in colon cancer cells by targeting NR4A/Sp complexes. This reveals a novel therapeutic strategy for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Orphan nuclear receptors NR4A1 and NR4A2 are overexpressed in solid tumors.
- These receptors promote tumor growth and MerTK expression.
Purpose of the Study:
- Investigate the effect of DIM-3,5 compounds on MerTK expression.
- Elucidate the regulatory mechanism of MerTK in colon cancer cells.
Main Methods:
- Utilized colon cancer cell lines (SW480, HCT116, CT26).
- Administered DIM-3,5 compounds and performed gene knockdown (NR4A1, NR4A2, Sp1, Sp3, Sp4).
- Employed chromatin immunoprecipitation and luciferase reporter assays.
Main Results:
- DIM-3,5 compounds significantly downregulated MerTK protein and RNA expression.
- NR4A1/NR4A2 knockdown decreased MerTK expression.
- MerTK expression is regulated by NR4A/Sp complexes (NR4A1, NR4A2, Sp1, Sp3, Sp4).
Conclusions:
- DIM-3,5 ligands act as novel inhibitors of MerTK expression in cancer cells.
- NR4A1 and NR4A2 participate in MerTK regulation.
- DIM-3,5 compounds represent a potential therapeutic strategy targeting MerTK in cancer.
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