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The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with β-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity.
Pubmed ID: 28467300
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsCommercial supplier of antibodies, reagents, and dyes for research.
View all literature mentionsA commercial antibody vendor, specializing in secondary antibodies.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsSoftware that manages the RNA-sequencing pipeline based on the TopHat suite of software automatically.
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
View all literature mentionsBiotechnology company in San Diego, California. Provides life scientists with innovative research reagents including immunity and cell culture products.
View all literature mentionsMus musculus with name Crl:NU(NCr)-Foxn1nu from IMSR.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
View all literature mentionsThis polyclonal targets Mouse Lipocalin-2 / NGAL
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal targets Chicken IgY (IgG) (H+L)
View all literature mentionsThis monoclonal targets Mouse Ly-6G / Ly-6C
View all literature mentionsThis monoclonal targets BrdU
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 monoclonal targets F4/80
View all literature mentionsThis unknown targets Prokaryotic recombinant fusion protein corresponding to a 1086bp Ki67 motif-containing cDNA fragment
View all literature mentionsThis monoclonal targets Lipocalin 2
View all literature mentionsThis recombinant monoclonal targets Lipocalin-2 / NGAL
View all literature mentionsThis monoclonal targets CD104
View all literature mentionsThis polyclonal targets Rabbit IgG (H+L)
View all literature mentionsThis monoclonal targets Myc-Tag
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis polyclonal targets IgG (H + L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis polyclonal targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG, whole molecule
View all literature mentionsThis polyclonal targets Keratin 5
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name FVB-Tg(KRT14-rtTA)F42Efu/J from IMSR.
View all literature mentionsCell line SRB-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SCC-13 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name Crl:SKH1-Hrhr from IMSR.
View all literature mentionsCell line SRB-12 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SCC-12 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name CrTac:NCr-Foxn1nu from IMSR.
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