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  1. Article: Increased Efficacy of Histone Methyltransferase G9a Inhibitors Against

    Bellamy, Jacob / Szemes, Marianna / Melegh, Zsombor / Dallosso, Anthony / Kollareddy, Madhu / Catchpoole, Daniel / Malik, Karim

    Frontiers in oncology

    2020  Volume 10, Page(s) 818

    Abstract: Targeted inhibition of proteins modulating epigenetic changes is an increasingly important priority in cancer therapeutics, and many small molecule inhibitors are currently being developed. In the case of neuroblastoma (NB), a pediatric solid tumor with ... ...

    Abstract Targeted inhibition of proteins modulating epigenetic changes is an increasingly important priority in cancer therapeutics, and many small molecule inhibitors are currently being developed. In the case of neuroblastoma (NB), a pediatric solid tumor with a paucity of intragenic mutations, epigenetic deregulation may be especially important. In this study we validate the histone methyltransferase G9a/EHMT2 as being associated with indicators of poor prognosis in NB. Immunological analysis of G9a protein shows it to be more highly expressed in NB cell-lines with
    Language English
    Publishing date 2020-05-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.00818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Wnt-BMP4 Signaling Axis Induces MSX and NOTCH Proteins and Promotes Growth Suppression and Differentiation in Neuroblastoma.

    Szemes, Marianna / Melegh, Zsombor / Bellamy, Jacob / Greenhough, Alexander / Kollareddy, Madhu / Catchpoole, Daniel / Malik, Karim

    Cells

    2020  Volume 9, Issue 3

    Abstract: The Wnt and bone morphogenetic protein (BMP) signaling pathways are known to be crucial in the development of neural crest lineages, including the sympathetic nervous system. Surprisingly, their role in paediatric neuroblastoma, the prototypic tumor ... ...

    Abstract The Wnt and bone morphogenetic protein (BMP) signaling pathways are known to be crucial in the development of neural crest lineages, including the sympathetic nervous system. Surprisingly, their role in paediatric neuroblastoma, the prototypic tumor arising from this lineage, remains relatively uncharacterised. We previously demonstrated that Wnt/b-catenin signaling can have cell-type-specific effects on neuroblastoma phenotypes, including growth inhibition and differentiation, and that BMP4 mRNA and protein were induced by Wnt3a/Rspo2. In this study, we characterised the phenotypic effects of BMP4 on neuroblastoma cells, demonstrating convergent induction of MSX homeobox transcription factors by Wnt and BMP4 signaling and BMP4-induced growth suppression and differentiation. An immunohistochemical analysis of BMP4 expression in primary neuroblastomas confirms a striking absence of BMP4 in poorly differentiated tumors, in contrast to a high expression in ganglion cells. These results are consistent with a tumor suppressive role for BMP4 in neuroblastoma. RNA sequencing following BMP4 treatment revealed induction of Notch signaling, verified by increases of Notch3 and Hes1 proteins. Together, our data demonstrate, for the first time, Wnt-BMP-Notch signaling crosstalk associated with growth suppression of neuroblastoma.
    MeSH term(s) Bone Morphogenetic Protein 4/metabolism ; Bone Morphogenetic Protein 4/pharmacology ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Homeodomain Proteins/metabolism ; Humans ; MSX1 Transcription Factor/metabolism ; Models, Biological ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Prognosis ; Receptor, Notch3/metabolism ; Signal Transduction ; Transcriptome/genetics ; Wnt Proteins/metabolism
    Chemical Substances Bone Morphogenetic Protein 4 ; Homeodomain Proteins ; MSX1 Transcription Factor ; MSX1 protein, human ; MSX2 protein ; NOTCH3 protein, human ; Receptor, Notch3 ; Wnt Proteins
    Language English
    Publishing date 2020-03-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9030783
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Transcriptomic Analyses of MYCN-Regulated Genes in Anaplastic Wilms' Tumour Cell Lines Reveals Oncogenic Pathways and Potential Therapeutic Vulnerabilities.

    Szemes, Marianna / Melegh, Zsombor / Bellamy, Jacob / Park, Ji Hyun / Chen, Biyao / Greenhough, Alexander / Catchpoole, Daniel / Malik, Karim

    Cancers

    2021  Volume 13, Issue 4

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2021-02-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13040656
    Database MEDical Literature Analysis and Retrieval System OnLINE

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