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Oncogene. 2017 Nov 23;36(47):6568-6580. doi: 10.1038/onc.2017.248. Epub 2017 Aug 7.

Glioblastoma stem cells exploit the αvβ8 integrin-TGFβ1 signaling axis to drive tumor initiation and progression.

Author information

1
Department of Neurosurgery, M. D. Anderson Cancer Center, Houston, TX, USA.
2
The Brown Institute for Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
3
Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX, USA.
4
Department of Genomic Medicine, M. D. Anderson Cancer Center, Houston, TX, USA.
5
Department of Translational Molecular Pathology, M. D. Anderson Cancer Center, Houston, TX, USA.
6
Departments of Pathology, M. D. Anderson Cancer Center, Houston, TX, USA.

Abstract

Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin αvβ8 and its latent transforming growth factor β1 (TGFβ1) protein ligand have central roles in promoting niche co-option and GBM initiation. αvβ8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of β8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that αvβ8 integrin regulates tumor development, in part, by driving TGFβ1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the αvβ8 integrin-TGFβ1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.

PMID:
28783169
PMCID:
PMC5882487
DOI:
10.1038/onc.2017.248
[Indexed for MEDLINE]
Free PMC Article

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