The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

Michael Pryszlak; Mallory Wiggans; Xin Chen; Julia E Jaramillo; Sarah E Burns; Laura M Richards; Trevor J Pugh; David R Kaplan; Xi Huang; Peter B Dirks; Bret J Pearson

doi:10.1016/j.celrep.2021.108903

The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

Cell Rep. 2021 Mar 30;34(13):108903. doi: 10.1016/j.celrep.2021.108903.

Authors

Affiliations

¹ The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON M5S 1A8, Canada.
² The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada.
³ Department of Medical Biophysics, University of Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.
⁴ Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Medical Biophysics, University of Toronto, ON M5G 1L7, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.
⁵ The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; The Hospital for Sick Children, Arthur and Sonia Labatt Brain Tumor Research Centre, Toronto, ON M5G 0A4, Canada.
⁶ The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 0A4, Canada; University of Toronto, Department of Molecular Genetics, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. Electronic address: bret.pearson@sickkids.ca.

PMID: 33789112
DOI: 10.1016/j.celrep.2021.108903

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.

Keywords: DDX56; RNAi; adult stem cells; cancer stem cells; comparative genomics; evolution of stem cells; glioblastoma; planarians; stemness.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
DEAD-box RNA Helicases / metabolism*
Drosophila / metabolism
Drosophila Proteins / metabolism
Gene Expression Regulation, Neoplastic
Genomics
Glioblastoma / genetics
Glioblastoma / pathology
HEK293 Cells
Humans
Mice
Models, Biological
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Neural Stem Cells / metabolism
Planarians / cytology
Planarians / metabolism
RNA Interference
Ribosome Subunits / metabolism
Treatment Outcome
Up-Regulation / genetics

Substances

Drosophila Proteins
DDX56 protein, human
DEAD-box RNA Helicases

Abstract

Publication types

MeSH terms

Substances

Grants and funding