Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells
- PMID: 24726434
- PMCID: PMC4004670
- DOI: 10.1016/j.cell.2014.02.030
Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells
Abstract
Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, and OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements and are sufficient to fully reprogram differentiated GBM cells to "induced" TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies candidate therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies. PAPERCLIP:
Copyright © 2014 Elsevier Inc. All rights reserved.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f5.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f6.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4004670/bin/nihms569762f7.gif)
Comment in
-
Connect four with glioblastoma stem cell factors.Cell. 2014 Apr 24;157(3):525-7. doi: 10.1016/j.cell.2014.04.001. Cell. 2014. PMID: 24766799
-
Cancer stem cells on demand.Nat Methods. 2014 Jul;11(7):715. doi: 10.1038/nmeth.3021. Nat Methods. 2014. PMID: 25110783 No abstract available.
Similar articles
-
SWIM tool application to expression data of glioblastoma stem-like cell lines, corresponding primary tumors and conventional glioma cell lines.BMC Bioinformatics. 2018 Nov 30;19(Suppl 15):436. doi: 10.1186/s12859-018-2421-x. BMC Bioinformatics. 2018. PMID: 30497369 Free PMC article.
-
Epigenetic modulation of metabolism in glioblastoma.Semin Cancer Biol. 2019 Aug;57:45-51. doi: 10.1016/j.semcancer.2018.09.002. Epub 2018 Sep 8. Semin Cancer Biol. 2019. PMID: 30205139 Review.
-
Changes in chromatin state reveal ARNT2 at a node of a tumorigenic transcription factor signature driving glioblastoma cell aggressiveness.Acta Neuropathol. 2018 Feb;135(2):267-283. doi: 10.1007/s00401-017-1783-x. Epub 2017 Nov 17. Acta Neuropathol. 2018. PMID: 29149419 Free PMC article.
-
Expression of the miR-302/367 cluster in glioblastoma cells suppresses tumorigenic gene expression patterns and abolishes transformation related phenotypes.Int J Cancer. 2015 Nov 15;137(10):2296-309. doi: 10.1002/ijc.29606. Epub 2015 Jun 5. Int J Cancer. 2015. PMID: 25991553 Free PMC article.
-
The emerging role of tumor-suppressive microRNA-218 in targeting glioblastoma stemness.Cancer Lett. 2014 Oct 10;353(1):25-31. doi: 10.1016/j.canlet.2014.07.011. Epub 2014 Jul 17. Cancer Lett. 2014. PMID: 25042866 Review.
Cited by
-
Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.J Hematol Oncol. 2024 May 8;17(1):31. doi: 10.1186/s13045-024-01544-7. J Hematol Oncol. 2024. PMID: 38720342 Free PMC article. Review.
-
Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.bioRxiv [Preprint]. 2024 Apr 27:2024.04.24.590852. doi: 10.1101/2024.04.24.590852. bioRxiv. 2024. PMID: 38712234 Free PMC article. Preprint.
-
Plasticity and resistance of cancer stem cells as a challenge for innovative anticancer therapies - do we know enough to overcome this?EXCLI J. 2024 Feb 29;23:335-355. doi: 10.17179/excli2024-6972. eCollection 2024. EXCLI J. 2024. PMID: 38655094 Free PMC article. Review.
-
Molecular diversity in isocitrate dehydrogenase-wild-type glioblastoma.Brain Commun. 2024 Mar 27;6(2):fcae108. doi: 10.1093/braincomms/fcae108. eCollection 2024. Brain Commun. 2024. PMID: 38646145 Free PMC article. Review.
-
Single-nucleus expression characterization of non-enhancing region of recurrent high-grade glioma.Neurooncol Adv. 2024 Jan 25;6(1):vdae005. doi: 10.1093/noajnl/vdae005. eCollection 2024 Jan-Dec. Neurooncol Adv. 2024. PMID: 38616896 Free PMC article.
References
-
- Anido J, Saez-Borderias A, Gonzalez-Junca A, Rodon L, Folch G, Carmona MA, Prieto-Sanchez RM, Barba I, Martinez-Saez E, Prudkin L, et al. TGF-beta Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma. Cancer cell. 2010;18:655–668. - PubMed
-
- Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–760. - PubMed
-
- Barrett LE, Granot Z, Coker C, Iavarone A, Hambardzumyan D, Holland EC, Nam HS, Benezra R. Self-renewal does not predict tumor growth potential in mouse models of high-grade glioma. Cancer cell. 2012;21:11–24. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials