Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

Stem Cells
Debolina GangulyLawrence M Pfeffer

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor that is refractory to existing therapeutic regimens, which reflects the presence of stem-like cells, termed glioma-initiating cells (GICs). The complex interactions between different signaling pathways and epigenetic regulation of key genes may be critical in the maintaining GICs in their stem-like state. Although several signaling pathways have been identified as being dysregulated in GBM, the prognosis of GBM patients remains miserable despite improvements in targeted therapies. In this report, we identified that BRG1, the catalytic subunit of the SWI/SNF chromatin remodeling complex, plays a fundamental role in maintaining GICs in their stem-like state. In addition, we identified a novel mechanism by which BRG1 regulates glycolysis genes critical for GICs. BRG1 downregulates the expression of TXNIP, a negative regulator of glycolysis. BRG1 knockdown also triggered the STAT3 pathway, which led to TXNIP activation. We further identified that TXNIP is an STAT3-regulated gene. Moreover, BRG1 suppressed the expression of interferon-stimulated genes, which are negatively regulated by STAT3 and regulate tumorigenesis. We further demonstrate that BRG1 pla...Continue Reading

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Citations

Mar 29, 2019·Pharmaceuticals·Debolina GangulyLawrence M Pfeffer
Nov 7, 2019·Diagnostic Pathology·Sergiu SusmanStefan Ioan Florian
Jun 4, 2020·Cancers·Carla Lucia EspositoVittorio de Franciscis
Feb 3, 2021·Journal of Cellular and Molecular Medicine·Yinan WangLawrence M Pfeffer
May 10, 2021·Bioorganic Chemistry·Xiuhong WeiFengyuan Che
Aug 8, 2021·International Journal of Molecular Sciences·Qiong WuArnold B Etame
Aug 14, 2021·Antioxidants & Redox Signaling·Hiroshi Masutani
Jun 21, 2021·Journal of Pathology and Translational Medicine·Anurag MehtaAnkush Jajodia
Jan 21, 2022·International Journal of Cancer. Journal International Du Cancer·Patrycja CzerwinskaAndrzej Adam Mackiewicz

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