title: Multiscale in situ analysis of the role of dyskerin in lung cancer cells.
abstract: Dyskerin is one of the three subunits of the telomerase ribonucleoprotein (RNP) complex. Very little is known about the role of dyskerin in the biology of the telomeres in cancer cells. In this study, we use a quantitative, multiscale 3D image-based in situ method and several molecular techniques to show that dyskerin is overexpressed in lung cancer cell lines. Furthermore, we show that dyskerin expression correlates with telomere length both at the cell population level--cells with higher dyskerin expression have short telomeres--and at the single cell level--the shortest telomeres of the cell are spatially associated with areas of concentration of dyskerin proteins. Using this in vitro model, we also show that exogenous increase in dyskerin expression confers resistance to telomere shortening caused by a telomerase inactivating drug. Finally, we show that resistance is achieved by the recovery of telomerase activity associated with dyskerin. In summary, using a novel multiscale image-based in situ method, we show that, in lung cancer cell lines, dyskerin responds to continuous telomere attrition by increasing the telomerase RNP activity, which in turn provides resistance to telomere shortening.
authors.affiliation: Oncology Division, Center for Applied Medical Research, CIMA, University of Navarra, Avda. Pio XII 55, Pamplona 31008, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernandez-Garcia
authors.forename: Tamara
authors.initials: T
authors.lastname: Marcos
authors.forename: Arrate
authors.initials: A
authors.lastname: Muñoz-Barrutia
authors.forename: Diego
authors.initials: D
authors.lastname: Serrano
authors.forename: Ruben
authors.initials: R
authors.lastname: Pio
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montuenga
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz-de-Solorzano
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics* / Q000648:ultrastructure; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure; D059506:Telomere Shortening / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D019098:Telomerase