1. The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells.
- Author
-
Pryszlak M, Wiggans M, Chen X, Jaramillo JE, Burns SE, Richards LM, Pugh TJ, Kaplan DR, Huang X, Dirks PB, and Pearson BJ
- Subjects
- Adult Stem Cells metabolism, Animals, Cell Line, Tumor, Cell Lineage, Cell Nucleolus metabolism, Cell Proliferation, Cell Self Renewal, Cell Survival, Cerebral Cortex cytology, DEAD-box RNA Helicases genetics, Drosophila metabolism, Drosophila Proteins metabolism, Gene Expression Regulation, Neoplastic, Genomics, Glioblastoma genetics, Glioblastoma pathology, HEK293 Cells, Humans, Mice, Models, Biological, Neoplastic Stem Cells pathology, Neural Stem Cells metabolism, Planarians cytology, Planarians metabolism, RNA Interference, Ribosome Subunits metabolism, Treatment Outcome, Up-Regulation genetics, DEAD-box RNA Helicases metabolism, Neoplastic Stem Cells metabolism
- Abstract
Across the animal kingdom, adult tissue homeostasis is regulated by adult stem cell activity, which is commonly dysregulated in human cancers. However, identifying key regulators of stem cells in the milieu of thousands of genes dysregulated in a given cancer is challenging. Here, using a comparative genomics approach between planarian adult stem cells and patient-derived glioblastoma stem cells (GSCs), we identify and demonstrate the role of DEAD-box helicase DDX56 in regulating aspects of stemness in four stem cell systems: planarians, mouse neural stem cells, human GSCs, and a fly model of glioblastoma. In a human GSC line, DDX56 localizes to the nucleolus, and using planarians, when DDX56 is lost, stem cells dysregulate expression of ribosomal RNAs and lose nucleolar integrity prior to stem cell death. Together, a comparative genomic approach can be used to uncover conserved stemness regulators that are functional in both normal and cancer stem cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF