title: ABCG1 maintains high-grade glioma survival in vitro and in vivo.
abstract: The overall survival for adults with malignant glioma (glioblastoma) remains poor despite advances in radiation and chemotherapy. One of the mechanisms by which cancer cells develop relative resistance to treatment is through de-regulation of endoplasmic reticulum (ER) homeostasis. We have recently shown that ABCG1, an ATP-binding cassette transporter, maintains ER homeostasis and suppresses ER stress-induced apoptosis in low-grade glioma. Herein, we demonstrate that ABCG1 expression is increased in human adult glioblastoma, where it correlates with poor survival in individuals with the mesenchymal subtype. Leveraging a mouse model of mesenchymal glioblastoma (NPcis), shRNA-mediated Abcg1 knockdown (KD) increased CHOP ER stress protein expression and resulted in greater NPcis glioma cell death in vitro. Moreover, Abcg1 KD reduced NPcis glioma growth and increased mouse survival in vivo. Collectively, these results demonstrate that ABCG1 is critical for malignant glioma cell survival, and might serve as a future therapeutic target for these deadly brain cancers.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cimino
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000378:metabolism*; D000328:Adult; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D005500:Follow-Up Studies; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060787:Neoplasm Grading; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D014408:Biomarkers, Tumor
keywords: ER stress; apoptosis; brain tumor; glioblastoma; glioma stem cell