SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Falk Lotta)
 

Sökning: WFRF:(Falk Lotta) > (2020) > PPM1D is a neurobla...

PPM1D is a neuroblastoma oncogene and therapeutic target in childhood neural tumors

Milosevic, Jelena (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, United States
Fransson, Susanne (författare)
Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Gulyas, Miklos, MD, PhD, Associate Professor, 1959- (författare)
Uppsala universitet,Klinisk och experimentell patologi
visa fler...
Gallo-Oller, Gabriel (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Olsen, Thale K (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Treis, Diana (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Wickström, Malin (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Elfman, Lotta HM (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Sveinbjornsson, Baldur (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Department of Medical Biology, University of Tromsö, Tromsö, Norway
Hertwig, Falk (författare)
Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Bartenhagen, Christoph (författare)
Department of Experimental Pediatric Oncology, University Children’s Hospital, Cologne, Germany; Center for Molecular Medicine (CMMC), Medical Faculty, University of Cologne, Cologne, Germany
Reinsbach, Susanne (författare)
Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Wilhelm, Margareta (författare)
Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm, Sweden
Abel, Frida (författare)
Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Javanmardi, Niloufar (författare)
Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Thankaswamy-Kosalai, Subazini (författare)
Department of Medical Genetics and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Eissler, Nina (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Kock, Anna (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Shi, Yao (författare)
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Tanino, Keiji (författare)
Laboratory of Organic Chemistry II, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Japan
Hehir-Kwa, Jane Y (författare)
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Mensenkamp, Arjen (författare)
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
Tytgat, Godelieve AM (författare)
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Kanduri, Chandrasekhar (författare)
Department of Medical Genetics and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Holmberg, Johan (författare)
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
Gisselsson, David (författare)
Department of Genetics and Pathology, University of Lund, Lund, Sweden
Molenaar, Jan J (författare)
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Jongmans, Marjolijn (författare)
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Fischer, Matthias (författare)
Department of Experimental Pediatric Oncology, University Children’s Hospital, Cologne, Germany; Center for Molecular Medicine (CMMC), Medical Faculty, University of Cologne, Cologne, Germany
Kool, Marcel (författare)
Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Sakaguchi, Kazuyasu (författare)
Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Japan
Baryawno, Ninib (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, USA
Martinsson, Tommy (författare)
Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
Johnsen, John Inge (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Kogner, Per (författare)
Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
visa färre...
 (creator_code:org_t)
Cold Spring Harbor Laboratory, 2020
Engelska.
Relaterad länk:
https://doi.org/10.1...
visa fler...
http://biorxiv.org/c...
https://uu.diva-port... (primary) (Raw object)
http://uu.diva-porta...
https://urn.kb.se/re...
https://doi.org/10.1...
visa färre...
  • Annan publikation (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Majority of cancers harbor alterations of the tumor suppressor TP53. However, childhood cancers, including unfavorable neuroblastoma, often lack TP53 mutations despite frequent loss of p53 function, suggesting alternative p53 inactivating mechanisms.Here we show that p53-regulating PPM1D at chromosome 17q22.3 is linked to aggressive tumors and poor prognosis in neuroblastoma. We identified that WIP1-phosphatase encoded by PPM1D, is activated by frequent segmental 17q-gain further accumulated during clonal evolution, gene-amplifications, gene-fusions or gain-of-function somatic and germline mutations. Pharmacological and genetic manipulation established WIP1 as a druggable target in neuroblastoma. Genome-scale CRISPR-Cas9 screening demonstrated PPM1D genetic dependency in TP53 wild-type neuroblastoma cell lines, and shRNA PPM1D knockdown significantly delayed in vivo tumor formation. Establishing a transgenic mouse model overexpressing PPM1D showed that these mice develop cancers phenotypically and genetically similar to tumors arising in mice with dysfunctional p53 when subjected to low-dose irradiation. Tumors include T-cell lymphomas harboring Notch1-mutations, Pten-deletions and p53-accumulation, adenocarcinomas and PHOX2B-expressing neuroblastomas establishing PPM1D as a bona fide oncogene in wtTP53 cancer and childhood neuroblastoma. Pharmacological inhibition of WIP1 suppressed the growth of neural tumors in nude mice proposing WIP1 as a therapeutic target in neural childhood tumors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)

Nyckelord

Patologi
Pathology

Publikations- och innehållstyp

vet (ämneskategori)
ovr (ämneskategori)

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy