Glioblastoma stem cells exploit the αvβ8 integrin-TGFβ1 signaling axis to drive tumor initiation and progression
| Autor: | Z. Chen, John E. Morales, F. F. Lang, Joseph H. McCarty, Erik P. Sulman, Qianghu Wang, Jeremy H. Tchaicha, Ganesh Rao, Greg Fuller, Nami McCarty, Paola A. Guerrero |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Integrins Integrin beta Chains Carcinogenesis Cellular differentiation Integrin Primary Cell Culture Tumor initiation Mice SCID Biology medicine.disease_cause Article Transforming Growth Factor beta1 03 medical and health sciences Mice Cell Line Tumor Genetics medicine Biomarkers Tumor Animals Humans AC133 Antigen Cell Self Renewal Molecular Biology Brain Neoplasms SOXB1 Transcription Factors Cell Differentiation Xenograft Model Antitumor Assays Cell biology 030104 developmental biology Cancer cell biology.protein Disease Progression Neoplastic Stem Cells M Phase Cell Cycle Checkpoints Stem cell Signal transduction Glioblastoma Transforming growth factor Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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