The aryl hydrocarbon receptor is a tumor suppressor-like gene in glioblastoma

Un Ho Jin, Keshav Karki, Yating Cheng, Sharon K. Michelhaugh, Sandeep Mittal, Stephen Safe

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) plays an important role in maintaining cellular homeostasis and also in pathophysiology. For example, the interplay between the gut microbiome and microbially derived AhR ligands protects against inflammation along the gut-brain axis. The AhR and its ligands also inhibit colon carcinogenesis, but it has been reported that the AhR and its ligand kynurenine enhance glioblastoma (GBM). In this study, using both established and patient-derivedGBMcells, we re-examined the role of kynurenine and the AhR in GBM, observing that kynurenine does not modulate AhR-mediated gene expression and does not affect invasion of GBM cells. Therefore, using an array of approaches, including ChIP, quantitative real-time PCR, and cell migration assays, we primarily focused on investigating the role of the AhR inGBMat the functional molecular and genomic levels. The results of transient and stable CRISPR/Cas9-mediated AhR knockdown in GBM cells indicated that loss of AhR enhances GBM tumor growth in a mouse xenograft model, increases GBM cell invasion, and upregulates expression of pro-invasion/pro-migration genes, as determined by ingenuity pathway analysis of RNA-Seq data.We conclude that the AhR is a tumor suppressor-like gene in GBM; future studies are required to investigate whether the AhR could be a potential drug target for treating patients with GBM who express this receptor.

Original languageEnglish (US)
Pages (from-to)11342-11353
Number of pages12
JournalJournal of Biological Chemistry
Volume294
Issue number29
DOIs
StatePublished - Jul 19 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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