Journal
ONCOTARGET
Volume 8, Issue 38, Pages 62962-62975Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18002
Keywords
DIPG; BMI-1; cell proliferation; cancer stem cells; therapeutic target
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Funding
- Joshua's Wish grant
- Division of Oncology
- Brain Tumor Center, Cincinnati Children's Hospital Medical Center, OH, USA
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Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells. BMI-1 downregulation leads to the inhibition of DIPG patient-derived neurosphere cell proliferation, cell cycle signaling, self-renewal, telomerase expression and activity, and suppresses DIPG cell migration. Moreover, targeted inhibition of BMI-1 sensitizes DIPG cells to radiomimetic drug-induced DNA damage. Together, our data validate BMI-1 as a potential therapeutic target to treat children with DIPG.
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