Role of AHR and HIF-1α in Glioblastoma Metabolism.
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling. AHR activity is regulated by tryptophan derivatives present in the tumor microenvironment. Thus, the tumor microenvironment and signaling via HIF-1α and AHR regulate the metabolism of gliomas and immune cells, modulating tumor-specific immunity and, consequently, tumor growth. Here, we review the roles of HIF-1α and AHR in cancer and immune cell metabolism in GBM.
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Galina
G
Gabriely
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Michael A
MA
Wheeler
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Maisa C
MC
Takenaka
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: fquintana@rics.bwh.harvard.edu.
Francisco J
FJ
Quintana
D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018336:Receptors, Aryl Hydrocarbon; D010100:Oxygen