Chemokine receptor CXCR4 interacts with nuclear receptor Nur77 and promote glioma invasion and progression

Brain Res. 2024 Jan 1:1822:148647. doi: 10.1016/j.brainres.2023.148647. Epub 2023 Oct 25.

Abstract

Background: Glioma is the most common primary brain tumor. It is prone to progress and have high rate of mortality regardless of radiation or chemotherapy due to its invasive growth features. Chemokine and its receptor CXCL12 and CXCR4 play important roles in cancer metastasis.

Methods: In this study, we investigate the role of CXCR4 in the progression of glioma by various molecular technologies, including qRT-PCR, Western blotting, wound closure assay, transwell assay et al. RESULTS: It was found that CXCR4 was overexpressed in glioma tissues. The expression of CXCR4 was correlated with patients' overall survival. Wound closure assay and transwell invasion assay showed that inhibition of CXCR4 significantly reduced the expression of biomarkers related to the formation of invadopodium, leading to decrease the invasion and migration of glioma tumor cells. Knocking down the nuclear receptor Nur77 remarkably decreased CXCR4 expression and reduced glioma cell invasion and migration. The reduction of glioma cell invasion and migration were observed after Nur77 inhibitor treatment.

Conclusion: Taken together, these results indicated that CXCR4 is critical in promoting glioma migration and invasion. Inhibition of Nur77 reduces CXCR4 related cancer progression.

Keywords: CXCR4; Glioma; Invasion; Nur77; Progression.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chemokine CXCL12 / metabolism
  • Glioma* / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Nuclear Receptor Subfamily 4, Group A, Member 1* / metabolism
  • Receptors, CXCR4* / metabolism
  • Receptors, Chemokine
  • Receptors, Cytoplasmic and Nuclear

Substances

  • Chemokine CXCL12
  • CXCR4 protein, human
  • Receptors, Chemokine
  • Receptors, CXCR4
  • Receptors, Cytoplasmic and Nuclear
  • Nuclear Receptor Subfamily 4, Group A, Member 1