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Cancer Cell. 2006 Sep;10(3):179-90.

Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling.

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  • 1Division of Cancer Immunology, Department of Pathology, and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210, USA.

Abstract

The genetic mechanisms responsible for increased incidence of lymphoma in immunocompromised individuals have not been fully elucidated. We show that, in a line of TCR transgenic TG-B mice, an insertional mutation in one allele of the Epm2a locus and epigenetic silencing of another led to a high rate of lymphoma with early onset. Overexpressing Epm2a suppressed the growth of established tumor cells and the development of lymphoma in the TG-B mice, while specific silencing of the locus increased tumorigenesis in the immune-deficient host. Downregulation of Epm2a expression is widespread among mouse and human lymphoma cell lines. Epm2a-encoded laforin is a phosphatase for GSK-3beta and an important repressor in the Wnt signaling pathway. Inactivation of Epm2a resulted in increased Wnt signaling and tumorigenesis.

PMID:
16959610
[PubMed - indexed for MEDLINE]
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