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Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 in stromal exosomes. After exosome transfer to immune cells, unshielded RN7SL1 drives an inflammatory response. Upon transfer to breast cancer cells, unshielded RN7SL1 activates the PRR RIG-I to enhance tumor growth, metastasis, and therapy resistance. Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer. VIDEO ABSTRACT.
Pubmed ID: 28709002 RIS Download
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Software package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsSoftware as R wrapper for Van der Maaten's Barnes-Hut implementation of t-Distributed Stochastic Neighbor Embedding. Used for high-dimentional data visualisation.
View all literature mentionsSoftware ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD274
View all literature mentionsThis monoclonal targets CD86
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets CD44
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets Human Notch4
View all literature mentionsThis recombinant monoclonal targets Notch2
View all literature mentionsThis polyclonal targets activated Notch1
View all literature mentionsThis monoclonal targets NOTCH1
View all literature mentionsThis monoclonal targets c-Myc antibody [Y69]
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets ISG15 (H-150)
View all literature mentionsThis monoclonal targets Rig-I
View all literature mentionsThis monoclonal targets Human POLR2A
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets TSG101
View all literature mentionsThis polyclonal targets SRP14
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
View all literature mentionsSoftware repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.
View all literature mentionsNetwork of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsCell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-468 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BJ [Human fibroblast] is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name NU/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6NCrl from IMSR.
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