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Published on: March 7, 2019
A genetic screen for candidate tumor suppressors identifies REST
Thomas F Westbrook1, Eric S Martin, Michael R Schlabach
1Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Researchers identified REST/NRSF as a novel tumor suppressor gene. Loss of REST promotes cancer by increasing PI(3)K signaling, offering new avenues for cancer gene discovery.
Area of Science:
- Cancer Biology
- Molecular Oncology
- Genetics
Background:
- Tumorigenesis involves complex genetic and epigenetic changes.
- Identifying key genes driving malignant transformation is crucial for cancer research.
Purpose of the Study:
- To identify genes suppressing malignant transformation in human mammary epithelial cells using an RNAi screen.
- To investigate the role of REST/NRSF in cancer development.
Main Methods:
- RNA interference (RNAi)-based genetic screen for transformation suppressors.
- Array comparative genomic hybridization (Array-CGH) for genetic alterations.
- Mutation analysis in colorectal cancer cells.
Main Results:
- Identified known tumor suppressors (TGFBR2, PTEN) and a novel suppressor, REST/NRSF.
- Found REST deletions in colorectal cancer and a transforming REST mutation.
- Demonstrated REST-deficient cells rely on PI(3)K signaling for transformation.
Conclusions:
- REST functions as a human tumor suppressor, previously unrecognized.
- REST loss contributes to cancer via PI(3)K pathway activation.
- This study provides a method for discovering novel cancer-suppressing genes.
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