title: ID2 promotes survival of glioblastoma cells during metabolic stress by regulating mitochondrial function.
abstract: Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria. ID2 suppression of ROS production reduced mitochondrial damage and enhanced tumor cell survival during glucose deprivation. Bioinformatics analysis of GBM gene expression data from The Cancer Genome Atlas (TCGA) database revealed that expression of ID2 mRNA is unique among ID gene family members in correlating with the expression of nuclear genes involved in mitochondrial energy metabolism and assembly of mETC. Our data indicate that the expression level of ID2 in GBM cells can predict the sensitivity of GBM-derived tumor cells to decreased glucose levels. Low levels of ID2 expression in human GBM tissues may identify a clinical group in which metabolic targeting of glycolytic pathways can be expected to have the greatest therapeutic efficacy.
authors.affiliation: Norris Cotton Cancer Center, Lebanon, NH 03756, USA.|Department of Pediatrics, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756, USA.|Department of Medicine, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756, USA.|Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Hanover, NH 03755, USA.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Hanover, NH 03755, USA.
authors.forename: Gilbert J
authors.identifier: 0000-0001-6060-1279
authors.initials: GJ
authors.lastname: Rahme
authors.affiliation: Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Hanover, NH 03755, USA.
authors.forename: Pranam D
authors.initials: PD
authors.lastname: Chatterjee
authors.affiliation: Norris Cotton Cancer Center, Lebanon, NH 03756, USA.|Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Hanover, NH 03755, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Havrda
authors.affiliation: Norris Cotton Cancer Center, Lebanon, NH 03756, USA.|Department of Pediatrics, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756, USA.|Department of Medicine, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756, USA.|Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Hanover, NH 03755, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Israel
mesh_terms: D045744:Cell Line, Tumor; D004734:Energy Metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D013312:Stress, Physiological; D016019:Survival Analysis
chemical_list: C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2