Glioblastoma stem cells exploit the ?v?8 integrin-TGF?1 signaling axis to drive tumor initiation and progression.

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 ?v?8 and its latent transforming growth factor ?1 (TGF?1) protein ligand have central roles in promoting niche co-option and GBM initiation. ?v?8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of ?8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that ?v?8 integrin regulates tumor development, in part, by driving TGF?1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the ?v?8 integrin-TGF?1 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.

SUBMITTER: Guerrero PA 

PROVIDER: S-EPMC5882487 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature