@article{GroebnerWorstWeischenfeldtetal.2018, author = {Gr{\"o}bner, Susanne N. and Worst, Barbara C. and Weischenfeldt, Joachim and Buchhalter, Ivo and Kleinheinz, Kortine and Rudneva, Vasilisa A. and Johann, Pascal D. and Balasubramanian, Gnana Prakash and Segura-Wang, Maia and Brabetz, Sebastian and Bender, Sebastian and Hutter, Barbara and Sturm, Dominik and Pfaff, Elke and H{\"u}bschmann, Daniel and Zipprich, Gideon and Heinold, Michael and Eils, J{\"u}rgen and Lawerenz, Christian and Erkek, Serap and Lambo, Sander and Waszak, Sebastian and Blattmann, Claudia and Borkhardt, Arndt and Kuhlen, Michaela and Eggert, Angelika and Fulda, Simone and Gessler, Manfred and Wegert, Jenny and Kappler, Roland and Baumhoer, Daniel and Stefan, Burdach and Kirschner-Schwabe, Renate and Kontny, Udo and Kulozik, Andreas E. and Lohmann, Dietmar and Hettmer, Simone and Eckert, Cornelia and Bielack, Stefan and Nathrath, Michaela and Niemeyer, Charlotte and Richter, G{\"u}nther H. and Schulte, Johannes and Siebert, Reiner and Westermann, Frank and Molenaar, Jan J. and Vassal, Gilles and Witt, Hendrik and Burkhardt, Birgit and Kratz, Christian P. and Witt, Olaf and van Tilburg, Cornelis M. and Kramm, Christof M. and Fleischhack, Gudrun and Dirksen, Uta and Rutkowski, Stefan and Fr{\"u}hwald, Michael and Hoff, Katja von and Wolf, Stephan and Klingebeil, Thomas and Koscielniak, Ewa and Landgraf, Pablo and Koster, Jan and Resnick, Adam C. and Zhang, Jinghui and Liu, Yanling and Zhou, Xin and Waanders, Angela J. and Zwijnenburg, Danny A. and Raman, Pichai and Brors, Benedikt and Weber, Ursula D. and Northcott, Paul A. and Pajtler, Kristian W. and Kool, Marcel and Piro, Rosario M. and Korbel, Jan O. and Schlesner, Matthias and Eils, Roland and Jones, David T. W. and Lichter, Peter and Chavez, Lukas and Zapatka, Marc and Pfister, Stefan M.}, title = {The landscape of genomic alterations across childhood cancers}, series = {Nature}, volume = {555}, journal = {Nature}, organization = {ICGC PedBrain-Seq Project, ICGC MMML-Seq Project,}, doi = {10.1038/nature25480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229579}, pages = {321-327}, year = {2018}, abstract = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8\% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50\% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.}, language = {en} } @article{MeierjohannHufnagelWendeetal.2010, author = {Meierjohann, Svenja and Hufnagel, Anita and Wende, Elisabeth and Kleinschmidt, Markus A. and Wolf, Katarina and Friedl, Peter and Gaubatz, Stefan and Schartl, Manfred}, title = {MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68335}, year = {2010}, abstract = {Background: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTKdriven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. Results: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. Conclusions: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.}, subject = {Medizin}, language = {en} } @article{HudsonNewboldContuetal.2014, author = {Hudson, Lawrence N. and Newbold, Tim and Contu, Sara and Hill, Samantha L. L. and Lysenko, Igor and De Palma, Adriana and Phillips, Helen R. P. and Senior, Rebecca A. and Bennett, Dominic J. and Booth, Hollie and Choimes, Argyrios and Correia, David L. P. and Day, Julie and Echeverria-Londono, Susy and Garon, Morgan and Harrison, Michelle L. K. and Ingram, Daniel J. and Jung, Martin and Kemp, Victoria and Kirkpatrick, Lucinda and Martin, Callum D. and Pan, Yuan and White, Hannah J. and Aben, Job and Abrahamczyk, Stefan and Adum, Gilbert B. and Aguilar-Barquero, Virginia and Aizen, Marcelo and Ancrenaz, Marc and Arbelaez-Cortes, Enrique and Armbrecht, Inge and Azhar, Badrul and Azpiroz, Adrian B. and Baeten, Lander and B{\´a}ldi, Andr{\´a}s and Banks, John E. and Barlow, Jos and Bat{\´a}ry, P{\´e}ter and Bates, Adam J. and Bayne, Erin M. and Beja, Pedro and Berg, Ake and Berry, Nicholas J. and Bicknell, Jake E. and Bihn, Jochen H. and B{\"o}hning-Gaese, Katrin and Boekhout, Teun and Boutin, Celine and Bouyer, Jeremy and Brearley, Francis Q. and Brito, Isabel and Brunet, J{\"o}rg and Buczkowski, Grzegorz and Buscardo, Erika and Cabra-Garcia, Jimmy and Calvino-Cancela, Maria and Cameron, Sydney A. and Cancello, Eliana M. and Carrijo, Tiago F. and Carvalho, Anelena L. and Castro, Helena and Castro-Luna, Alejandro A. and Cerda, Rolando and Cerezo, Alexis and Chauvat, Matthieu and Clarke, Frank M. and Cleary, Daniel F. R. and Connop, Stuart P. and D'Aniello, Biagio and da Silva, Pedro Giovani and Darvill, Ben and Dauber, Jens and Dejean, Alain and Diek{\"o}tter, Tim and Dominguez-Haydar, Yamileth and Dormann, Carsten F. and Dumont, Bertrand and Dures, Simon G. and Dynesius, Mats and Edenius, Lars and Elek, Zolt{\´a}n and Entling, Martin H. and Farwig, Nina and Fayle, Tom M. and Felicioli, Antonio and Felton, Annika M. and Ficetola, Gentile F. and Filgueiras, Bruno K. C. and Fonte, Steve J. and Fraser, Lauchlan H. and Fukuda, Daisuke and Furlani, Dario and Ganzhorn, J{\"o}rg U. and Garden, Jenni G. and Gheler-Costa, Carla and Giordani, Paolo and Giordano, Simonetta and Gottschalk, Marco S. and Goulson, Dave and Gove, Aaron D. and Grogan, James and Hanley, Mick E. and Hanson, Thor and Hashim, Nor R. and Hawes, Joseph E. and H{\´e}bert, Christian and Helden, Alvin J. and Henden, John-Andr{\´e} and Hern{\´a}ndez, Lionel and Herzog, Felix and Higuera-Diaz, Diego and Hilje, Branko and Horgan, Finbarr G. and Horv{\´a}th, Roland and Hylander, Kristoffer and Horv{\´a}th, Roland and Isaacs-Cubides, Paola and Ishitani, Mashiro and Jacobs, Carmen T. and Jaramillo, Victor J. and Jauker, Birgit and Jonsell, Matts and Jung, Thomas S. and Kapoor, Vena and Kati, Vassiliki and Katovai, Eric and Kessler, Michael and Knop, Eva and Kolb, Annette and K{\"o}r{\"o}si, {\`A}d{\´a}m and Lachat, Thibault and Lantschner, Victoria and Le F{\´e}on, Violette and LeBuhn, Gretchen and L{\´e}gar{\´e}, Jean-Philippe and Letcher, Susan G. and Littlewood, Nick A. and L{\´o}pez-Quintero, Carlos A. and Louhaichi, Mounir and L{\"o}vei, Gabor L. and Lucas-Borja, Manuel Esteban and Luja, Victor H. and Maeto, Kaoru and Magura, Tibor and Mallari, Neil Aldrin and Marin-Spiotta, Erika and Marhall, E. J. P. and Mart{\´i}nez, Eliana and Mayfield, Margaret M. and Mikusinski, Gregorz and Milder, Jeffery C. and Miller, James R. and Morales, Carolina L. and Muchane, Mary N. and Muchane, Muchai and Naidoo, Robin and Nakamura, Akihiro and Naoe, Shoji and Nates-Parra, Guiomar and Navarerete Gutierrez, Dario A. and Neuschulz, Eike L. and Noreika, Norbertas and Norfolk, Olivia and Noriega, Jorge Ari and N{\"o}ske, Nicole M. and O'Dea, Niall and Oduro, William and Ofori-Boateng, Caleb and Oke, Chris O. and Osgathorpe, Lynne M. and Paritsis, Juan and Parrah, Alejandro and Pelegrin, Nicol{\´a}s and Peres, Carlos A. and Persson, Anna S. and Petanidou, Theodora and Phalan, Ben and Philips, T. Keith and Poveda, Katja and Power, Eileen F. and Presley, Steven J. and Proen{\c{c}}a, V{\^a}nia and Quaranta, Marino and Quintero, Carolina and Redpath-Downing, Nicola A. and Reid, J. Leighton and Reis, Yana T. and Ribeiro, Danilo B. and Richardson, Barbara A. and Richardson, Michael J. and Robles, Carolina A. and R{\"o}mbke, J{\"o}rg and Romero-Duque, Luz Piedad and Rosselli, Loreta and Rossiter, Stephen J. and Roulston, T'ai H. and Rousseau, Laurent and Sadler, Jonathan P. and S{\´a}fi{\´a}n, Szbolcs and Salda{\~n}a-V{\´a}squez, Romeo A. and Samneg{\aa}rd, Ulrika and Sch{\"u}epp, Christof and Schweiger, Oliver and Sedlock, Jodi L. and Shahabuddin, Ghazala and Sheil, Douglas and Silva, Fernando A. B. and Slade, Eleanor and Smith-Pardo, Allan H. and Sodhi, Navjot S. and Somarriba, Eduardo J. and Sosa, Ram{\´o}n A. and Stout, Jane C. and Struebig, Matthew J. and Sung, Yik-Hei and Threlfall, Caragh G. and Tonietto, Rebecca and T{\´o}thm{\´e}r{\´e}sz, B{\´e}la and Tscharntke, Teja and Turner, Edgar C. and Tylianakis, Jason M. and Vanbergen, Adam J. and Vassilev, Kiril and Verboven, Hans A. F. and Vergara, Carlos H. and Vergara, Pablo M. and Verhulst, Jort and Walker, Tony R. and Wang, Yanping and Watling, James I. and Wells, Konstans and Williams, Christopher D. and Willig, Michael R. and Woinarski, John C. Z. and Wolf, Jan H. D. and Woodcock, Ben A. and Yu, Douglas W. and Zailsev, Andreys and Collen, Ben and Ewers, Rob M. and Mace, Georgina M. and Purves, Drew W. and Scharlemann, J{\"o}rn P. W. and Pervis, Andy}, title = {The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts}, series = {Ecology and Evolution}, volume = {4}, journal = {Ecology and Evolution}, number = {24}, doi = {10.1002/ece3.1303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114425}, pages = {4701 - 4735}, year = {2014}, abstract = {Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1\% of the total number of all species described, and more than 1\% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.}, language = {en} } @article{SimonRauskolbGunnersenetal.2015, author = {Simon, Christian M. and Rauskolb, Stefanie and Gunnersen, Jennifer M. and Holtmann, Bettina and Drepper, Carsten and Dombert, Benjamin and Braga, Massimiliano and Wiese, Stefan and Jablonka, Sibylle and P{\"u}hringer, Dirk and Zielasek, J{\"u}rgen and Hoeflich, Andreas and Silani, Vincenzo and Wolf, Eckhard and Kneitz, Susanne and Sommer, Claudia and Toyka, Klaus V. and Sendtner, Michael}, title = {Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy}, series = {Acta Neuropathologica}, volume = {130}, journal = {Acta Neuropathologica}, doi = {10.1007/s00401-015-1446-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154569}, pages = {373 -- 387}, year = {2015}, abstract = {Diabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen in DNP. Motor axon degeneration was also observed in mice in which the IGF1 receptor(IGF1R) was conditionally depleted in motoneurons, indicating that reduced activity of IGF1 on IGF1R in motoneurons is responsible for the observed effect. These data provide evidence that elevated expression of IGFBP5 in diabetic nerves reduces the availability of IGF1 for IGF1R on motor axons, thus leading to progressive neurodegeneration. Inhibition of IGFBP5 could thus offer novel treatment strategies for DNP.}, language = {en} } @article{PattschullWalzGruendletal.2019, author = {Pattschull, Grit and Walz, Susanne and Gr{\"u}ndl, Marco and Schwab, Melissa and R{\"u}hl, Eva and Baluapuri, Apoorva and Cindric-Vranesic, Anita and Kneitz, Susanne and Wolf, Elmar and Ade, Carsten P. and Rosenwald, Andreas and von Eyss, Bj{\"o}rn and Gaubatz, Stefan}, title = {The Myb-MuvB complex is required for YAP-dependent transcription of mitotic genes}, series = {Cell Reports}, volume = {27}, journal = {Cell Reports}, number = {12}, doi = {10.1016/j.celrep.2019.05.071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202039}, pages = {3533-3546}, year = {2019}, abstract = {YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here, we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes coactivated by YAP and B-MYB is associated with poor survival of cancer patients. Our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways.}, language = {en} }