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Author  |
Guerrero, P.A.; Tchaicha, J.H.; Chen, Z.; Morales, J.E.; McCarty, N.; Wang, Q.; Sulman, E.P.; Fuller, G.; Lang, F.F.; Rao, G.; McCarty, J.H. |

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Title |
Glioblastoma stem cells exploit the alphavbeta8 integrin-TGFbeta1 signaling axis to drive tumor initiation and progression |
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Journal Article |
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Year |
2017 |
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Oncogene |
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Oncogene |
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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 alphavbeta8 and its latent transforming growth factor beta1 (TGFbeta1) protein ligand have central roles in promoting niche co-option and GBM initiation. alphavbeta8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of beta8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that alphavbeta8 integrin regulates tumor development, in part, by driving TGFbeta1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the alphavbeta8 integrin-TGFbeta1 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.Oncogene advance online publication, 7 August 2017; doi:10.1038/onc.2017.248. |
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Department of Neurosurgery, M. D. Anderson Cancer Center, Houston, TX, USA |
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English |
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0950-9232 |
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PMID:28783169 |
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96572 |
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