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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Katz, Shauna Nagourney, Robert Carson, Brittany B. Brown, Anthony M. C. Klein, Keren Cardozo, Timothy Dasgupta, Ramanuj Evans, Steve Gonsalves, Foster C. Ekas, Laura A. |
| Description | Author Affiliation: Gonsalves FC ( Department of Pharmacology and New York University Cancer Institute, New York University Langone Medical Center, New York, NY 10016, USA.); |
| Abstract | Misregulated ß-catenin responsive transcription (CRT) has been implicated in the genesis of various malignancies, including colorectal carcinomas, and it is a key therapeutic target in combating various cancers. Despite significant effort, successful clinical implementation of CRT inhibitory therapeutics remains a challenging goal. This is, in part, because of the challenge of identifying inhibitory compounds that specifically modulate the nuclear transcriptional activity of ß-catenin while not affecting its cytoskeletal function in stabilizing adherens junctions at the cell membrane. Here, we report an RNAi-based modifier screening strategy for the identification of CRT inhibitors. Our data provide support for the specificity of these inhibitory compounds in antagonizing the transcriptional function of nuclear ß-catenin. We show that these inhibitors efficiently block Wnt/ß-catenin-induced target genes and phenotypes in various mammalian and cancer cell lines. Importantly, these Wnt inhibitors are specifically cytotoxic to human colon tumor biopsy cultures as well as colon cancer cell lines that exhibit deregulated Wnt signaling. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antineoplastic Agents Chemistry Drug Discovery RNA Interference Transcription, Genetic Drug Effects Wnt Proteins Antagonists & Inhibitors Beta Catenin Animals Isolation & Purification Therapeutic Use Cell Line, Tumor Colonic Neoplasms Drug Therapy Drosophila Proteins Genetics Drosophila Melanogaster Drug Screening Assays, Antitumor Genes, Reporter High-Throughput Screening Assays Mice Oxazoles Small Molecule Libraries Wnt1 Protein Xenograft Model Antitumor Assays Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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