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Autophagy-related factors are implicated in metabolic adaptation and cancer metastasis. However, the role of autophagy factors in cancer progression and their effect in treatment response remain largely elusive. Recent studies have shown that UVRAG, a key autophagic tumour suppressor, is mutated in common human cancers. Here we demonstrate that the cancer-related UVRAG frameshift (FS), which does not result in a null mutation, is expressed as a truncated UVRAG(FS) in colorectal cancer (CRC) with microsatellite instability (MSI), and promotes tumorigenesis. UVRAG(FS) abrogates the normal functions of UVRAG, including autophagy, in a dominant-negative manner. Furthermore, expression of UVRAG(FS) can trigger CRC metastatic spread through Rac1 activation and epithelial-to-mesenchymal transition, independently of autophagy. Interestingly, UVRAG(FS) expression renders cells more sensitive to standard chemotherapy regimen due to a DNA repair defect. These results identify UVRAG as a new MSI target gene and provide a mechanism for UVRAG participation in CRC pathogenesis and treatment response.
Pubmed ID: 26234763 RIS Download
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An extensible and customizable gene annotation portal that emphasizes community extensibility and user customizability. It is a complete resource for learning about gene and protein function. Community extensibility reflects a belief that any BioGPS user should be able to add new content to BioGPS using the simple plugin interface, completely independently of the core developer team. User customizability recognizes that not all users are interested in the same set of gene annotation data, so the gene report layouts enable each user to define the information that is most relevant to them. Currently, BioGPS supports eight species: Human (Homo sapiens), Mouse (Mus musculus), Rat (Rattus norvegicus), Fruitfly (Drosophila melanogaster), Nematode (Caenorhabditis elegans), Zebrafish (Danio rerio), Thale-cress (Arabidopsis thaliana), Frog (Xenopus tropicalis), and Pig (Sus scrofa). BioGPS presents data in an ortholog-centric format, which allows users to display mouse plugins next to human ones. Our data for defining orthologs comes from NCBI's HomoloGene database.
View all literature mentionsA software package for visualizing data and information. It visualizes data in a circular layout - this makes Circos ideal for exploring relationships between objects or positions.
View all literature mentionsA portal that provides visualization, analysis and download of large-scale cancer genomics data sets.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HCT 15 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line SW480 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 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 mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsNational public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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