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Squamous cell carcinomas occurring at transition zones are highly malignant tumors with poor prognosis. The identity of the cell population and the signaling pathways involved in the progression of transition zone squamous cell carcinoma are poorly understood, hence representing limited options for targeted therapies. Here, we identify a highly tumorigenic cancer stem cell population in a mouse model of transitional epithelial carcinoma and uncover a novel mechanism by which loss of TGFβ receptor II (Tgfbr2) mediates invasion and metastasis through de-repression of ELMO1, a RAC-activating guanine exchange factor, specifically in cancer stem cells of transition zone tumors. We identify ELMO1 as a novel target of TGFβ signaling and show that restoration of Tgfbr2 results in a complete block of ELMO1 in vivo. Knocking down Elmo1 impairs metastasis of carcinoma cells to the lung, thereby providing insights into the mechanisms of progression of Tgfbr2-deficient invasive transition zone squamous cell carcinoma.
Pubmed ID: 28219480 RIS Download
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A tool for performing multi-cluster gene functional enrichment analyses on large scale data (microarray experiments with many time-points, cell-types, tissue-types, etc.). It facilitates co-analysis of multiple gene lists and yields as output a rich functional map showing the shared and list-specific functional features. The output can be visualized in tabular, heatmap or network formats using built-in options as well as third-party software. It uses the hypergeometric test to obtain functional enrichment achieved via the gene list enrichment analysis option available in ToppGene.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
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View all literature mentionsAn Antibody supplier who also provides assay services and products.
View all literature mentionslaboratory mouse with name C57BL/6N from MGI.
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis polyclonal targets Phospho-Smad2 (Ser465/467)
View all literature mentionsThis polyclonal targets Phospho-Smad2 (Ser465/467)
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD49f (Integrin α6 chain)
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD49f (Integrin α6 chain)
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