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Glioblastoma (GBM) is highly refractory to therapy and associated with poor clinical outcome. Here, we reveal a critical function of the promitotic and adhesion-mediating discoidin domain receptor 1 (DDR1) in modulating GBM therapy resistance. In GBM cultures and clinical samples, we show a DDR1 and GBM stem cell marker co-expression that correlates with patient outcome. We demonstrate that inhibition of DDR1 in combination with radiochemotherapy with temozolomide in GBM models enhances sensitivity and prolongs survival superior to conventional therapy. We identify a 14-3-3-Beclin-1-Akt1 protein complex assembling with DDR1 to be required for prosurvival Akt and mTOR signaling and regulation of autophagy-associated therapy sensitivity. Our results uncover a mechanism driven by DDR1 that controls GBM therapy resistance and provide a rationale target for the development of therapy-sensitizing agents.
Pubmed ID: 30917320 RIS Download
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Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsSoftware that detects kinase-specific phosphorylation sites. GPS provides a platform able to perform its prediction based on a group-based phosphorylation scoring algorithm. It allows users to query multiple protein sequences through a batch prediction mode.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsThis monoclonal targets Musashi-1
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets SOX2 antibody [9-9-3]
View all literature mentionsThis polyclonal targets EasyBlot anti Rabbit IgG(HRP)
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis monoclonal targets nestin (10c2)
View all literature mentionsThis unknown targets GST
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets slightly modified β-cytoplasmic actin N-terminal peptide, Ac-Asp-Asp-Asp-Ile-Ala-Ala-Leu-Val-Ile-Asp-Asn-Gly-Ser-Gly-Lys, conjugated to KLH
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis unknown targets normal rabbit IgG
View all literature mentionsThis unknown targets mTOR, phospho (Ser2481)
View all literature mentionsThis monoclonal targets Rictor (53A2) Rabbit mAb
View all literature mentionsThis monoclonal targets mTOR
View all literature mentionsThis monoclonal targets Raptor (24C12) Rabbit mAb
View all literature mentionsThis polyclonal targets sox2
View all literature mentionsThis monoclonal targets CASP8
View all literature mentionsThis monoclonal targets DDR1 (D1G6) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis unknown targets Human Caspase 9
View all literature mentionsThis monoclonal targets Akt1
View all literature mentionsThis polyclonal targets
View all literature mentionsThis polyclonal targets 14-3-3 antibody
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets 14-3-3 (pan)
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsCell line U-138MG is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-172 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionslaboratory mouse with name NMRI-Foxn1nu from MGI.
View all literature mentionsCell line U-343MG is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-87MG ATCC is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line LN-229 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-138MG is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-172 is a Cancer cell line with a species of origin Homo sapiens (Human)
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