title: Caspase-8 is essential for maintaining chromosomal stability and suppressing B-cell lymphomagenesis.
abstract: In addition to its proapoptotic function, caspase-8 is also important for several other processes, including suppressing necroptosis, cell migration, and immune cell survival. In the present study, we report that the loss of caspase-8 in B lymphocytes leads to B-cell malignancies and that the risk for these tumors is further enhanced in the absence of p53. We also report that deficiency of caspase-8 results in impaired cytokinesis and that casp8(-/-) lymphomas display remarkably elevated levels of chromosomal aberrations. Our data support an important role for caspase-8 in the maintenance of genomic integrity and highlight its tumor-suppressive function.
authors.affiliation: Department of Medical Biophysics, University of Toronto and Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. ahakem@uhnres.utoronto.ca
authors.forename: Anne
authors.initials: A
authors.lastname: Hakem
authors.forename: Samah
authors.initials: S
authors.lastname: El Ghamrasni
authors.forename: Georges
authors.initials: G
authors.lastname: Maire
authors.forename: Benedicte
authors.initials: B
authors.lastname: Lemmers
authors.forename: Jana
authors.initials: J
authors.lastname: Karaskova
authors.forename: Andrea
authors.initials: A
authors.lastname: Jurisicova
authors.forename: Otto
authors.initials: O
authors.lastname: Sanchez
authors.forename: Jeremy
authors.initials: J
authors.lastname: Squire
authors.forename: Razqallah
authors.initials: R
authors.lastname: Hakem
mesh_terms: D016475:3T3 Cells; D000818:Animals; D056735:Autoimmune Lymphoproliferative Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D053181:Caspase 8 / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D043171:Chromosomal Instability / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D016158:Genes, p53 / Q000502:physiology; D020022:Genetic Predisposition to Disease; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016019:Survival Analysis
chemical_list: C505526:Casp8 protein, mouse; D053181:Caspase 8