title: Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma.
abstract: Distinct molecular pathways could be constitutively active in mouse T-Antigen positive and T-Antigen negative medulloblastoma cell lines, contributing to their phenotypic differences as well as to cellular responses, cell cycle progression, cell death and survival. The diversity of these responses may be due, at least in part, to distinct activities of Rb2/p130, CTCF and BORIS proteins in response to an altered network of signaling evoked by the T-Ag presence. Here, we provided evidence supporting a role for the T-Antigen in causing chronic endoplasmic reticulum (ER) stress and aberrant Caspase-12 expression and activation, subsequently driving to both massive cell death, and perhaps selection of cells with a higher malignant phenotype. Furthermore, we observed that the endoplasmic stress, either chronically caused by T-Ag or transiently induced by glucose deprivation, is accompanied by the formation of complexes between the retinoblastoma related protein Rb2/p130 and the chromatin insulator CCCTC-binding factor CTCF, or the CTCF-paralogue BORIS. Our study represents the first evidence supporting a role of the T-Antigen in inducing/maintaining chronic ER-stress, as well as, indicating a role of Rb2/p130, CTCF and BORIS as potential mediators of non-canonical ER-dependent death pathway in mouse medulloblastoma.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Valentina
authors.initials: V
authors.lastname: Caracciolo
authors.forename: Valeria
authors.initials: V
authors.lastname: Rizzo
authors.forename: Ang
authors.initials: A
authors.lastname: Sun
authors.forename: Micaela
authors.initials: M
authors.lastname: Montanari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Russo
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Bellipanni
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D017209:Apoptosis; D000076246:CCCTC-Binding Factor; D053454:Caspase 12 / Q000378:metabolism; D016923:Cell Death; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D000957:Antigens, Viral, Tumor; D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; C493838:Rbl2 protein, mouse; D012097:Repressor Proteins; D050717:Retinoblastoma-Like Protein p130; C506440:Casp12 protein, mouse; D053454:Caspase 12; D005947:Glucose