title: Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling.
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.
authors.affiliation: Division of Cancer Immunology, Department of Pathology, and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio 43210, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Cindy
authors.initials: C
authors.lastname: Wu
authors.forename: Huiming
authors.initials: H
authors.lastname: Zhang
authors.forename: Xincheng
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Terrence L
authors.initials: TL
authors.lastname: Geiger
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019175:DNA Methylation; D054637:Dual-Specificity Phosphatases; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015398:Signal Transduction; D015996:Survival Rate; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D011948:Receptors, Antigen, T-Cell; D051153:Wnt Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D054637:Dual-Specificity Phosphatases; C491989:Epm2a protein, mouse; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C114990:EPM2A protein, human