Monday, 9th May 2011

An RNAi-based Chemical Genetic Screen Identifies Three Small-Molecule Inhibitors of the Wnt/wingless Signaling Pathway

Source: National Academy of Sciences

From the abstract:

Misregulated β-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 β-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 β-catenin. We show that these inhibitors efficiently block Wnt/β-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.

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Category:

• Health and healthcare (DocuTicker)
• Science (DocuTicker)

Source:

• National Academy of Sciences

Views: 1294

By Heather Negley

An Info Pro, librarian, entrepreneur, author, worldwide connector and book-lover, Heather Negley is recognized for her new ways of thinking about librarianship, research, social media and creativity. Heather is the founder of HelpALibrarian.com and Zing Information Services. She has most recently been an Information Research Specialist with the Congressional Research Service at the Library of Congress where she provided business research for members of Congress and their staffs. Heather also worked as a research reporter for U.S. News and World Report and as a technical advertising producer on the washingtonpost.com. She received her MS in Library and Information Science from Simmons College in Boston, MA.

Heather can be reached at heather.negley@freepint.com

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