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An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.

Publication ,  Journal Article
Rheinbay, E; Suvà, ML; Gillespie, SM; Wakimoto, H; Patel, AP; Shahid, M; Oksuz, O; Rabkin, SD; Martuza, RL; Rivera, MN; Louis, DN; Kasif, S ...
Published in: Cell Rep
May 30, 2013

Glioblastoma (GBM) is thought to be driven by a subpopulation of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity yet remain poorly understood. Here, we present a comparative analysis of chromatin state in GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for the maintenance and in vivo tumorigenicity of GBM CSCs. Genome-wide binding profiles for ASCL1 and the Wnt effector LEF-1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections among ASCL1, Wnt signaling, and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 30, 2013

Volume

3

Issue

5

Start / End Page

1567 / 1579

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Wnt Proteins
  • Tumor Cells, Cultured
  • RNA, Small Interfering
  • RNA Interference
  • Neoplastic Stem Cells
  • Lymphoid Enhancer-Binding Factor 1
  • Intercellular Signaling Peptides and Proteins
  • Humans
  • Glioblastoma
 

Citation

APA
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Rheinbay, E., Suvà, M. L., Gillespie, S. M., Wakimoto, H., Patel, A. P., Shahid, M., … Bernstein, B. E. (2013). An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep, 3(5), 1567–1579. https://doi.org/10.1016/j.celrep.2013.04.021
Rheinbay, Esther, Mario L. Suvà, Shawn M. Gillespie, Hiroaki Wakimoto, Anoop P. Patel, Mohammad Shahid, Ozgur Oksuz, et al. “An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.Cell Rep 3, no. 5 (May 30, 2013): 1567–79. https://doi.org/10.1016/j.celrep.2013.04.021.
Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, et al. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep. 2013 May 30;3(5):1567–79.
Rheinbay, Esther, et al. “An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.Cell Rep, vol. 3, no. 5, May 2013, pp. 1567–79. Pubmed, doi:10.1016/j.celrep.2013.04.021.
Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep. 2013 May 30;3(5):1567–1579.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

May 30, 2013

Volume

3

Issue

5

Start / End Page

1567 / 1579

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Wnt Proteins
  • Tumor Cells, Cultured
  • RNA, Small Interfering
  • RNA Interference
  • Neoplastic Stem Cells
  • Lymphoid Enhancer-Binding Factor 1
  • Intercellular Signaling Peptides and Proteins
  • Humans
  • Glioblastoma