Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth.

Cell | Nov 17, 2016

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

Pubmed ID: 27863244 RIS Download

Mesh terms: Endothelial Cells | Epigenomics | Gene Expression Regulation, Neoplastic | Glioblastoma | Homeodomain Proteins | Humans | Neoplasm Invasiveness | Neural Stem Cells | PAX6 Transcription Factor | Proto-Oncogene Proteins c-akt | Transcription Factors | Wnt-5a Protein

Research resources used in this publication

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P30 CA016672
  • Agency: NCI NIH HHS, Id: P01 CA095616
  • Agency: NCI NIH HHS, Id: K99 CA194289
  • Agency: NCI NIH HHS, Id: P50 CA097257
  • Agency: NCI NIH HHS, Id: P50 CA127001

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


FlowJo

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

tool

View all literature mentions

ImageJ

Software tool as an open source Java-based image processing program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

tool

View all literature mentions

R Tutorial - An R Introduction to Statistics

A couple of introductory tutorials on basic R concepts that provides an introduction to the R programming language, and illustrates its use by solving elementary statistics textbook exercises. Beyond the basics, they also cover topics of GPU computing in R. An R Tutorial eBook is also available.

tool

View all literature mentions

Integrative Genomics Viewer

A high-performance visualization tool for interactive exploration of large, integrated genomic datasets.

tool

View all literature mentions

Pannoramic Viewer

Virtual microscope software that enables users to view samples and to make annotations and measurements. Users can change magnification of one or multiple slides at once, as well as change brightness, contrast, and color bias in real time. Images can be captured in JPG, BMP, and TIFF format, and slides can be exported to be compatible with Axiovision software.

tool

View all literature mentions