Journal
ONCOTARGET
Volume 7, Issue 17, Pages 23416-23424Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8030
Keywords
glioblastoma; ER stress; brain tumor; glioma stem cell; apoptosis
Categories
Funding
- National Institutes of Health [R01-NS065547, P50-CA094056]
- American Brain Tumor Association by the Emily Dorfman Foundation for Children
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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.
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