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dc.contributor.authorMerve, Ashirwad J.
dc.date.accessioned2015-08-25T15:42:38Z
dc.date.available2015-08-25T15:42:38Z
dc.date.issued2014
dc.identifier.citationMerve,A.J. 2014. BMI1-BMP Connection in Medulloblastoma Pathogenesis. Queen Mary University of Londonen_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8304
dc.descriptionPhDen_US
dc.description.abstractMedulloblastoma (MB) is the commonest intracranial childhood malignancy and despite recent advances, current therapeutic approaches are still associated with high morbidity and mortality. A novel molecular classification has recently been proposed for these tumours – WNT Group (best prognosis), SHH Group (intermediate prognosis), Group 3 (worst prognosis) and Group 4 (intermediate prognosis). BMI1, a transcriptional repressor of the Polycomb group genes, is overexpressed in MB, most significantly in those of Group 4 MBs. Bone Morphogenetic Proteins (BMPs) are morphogens belonging to TGF-β superfamily of growth factors, and are known to inhibit MB cell proliferation and induce apoptosis in vitro, and to inhibit tumour growth in vivo. Our team have recently demonstrated that Bmi1 regulates cell adhesion properties during cerebellar development through repression of the BMP pathway. The aim of this project is to assess whether BMI1 overexpression may contribute to MB pathogenesis through repression of the BMP pathway. Here we demonstrate that BMI1 knock down derepresses BMP pathway, and using a novel xenograft model of human MB of Group 4, we show that BMI1 controls tumour volume and intraparenchymal invasion. In in vitro assays on MB cell lines we show that cell adhesion and motility is controlled by BMI1 in a BMP dependent manner and that deregulation of extracellular matrix proteins are key mediators of this effect. Furthermore, we demonstrate that BMP treatment to BMI1 overexpressing MB cells reduces cell proliferation and invasion, suggesting BMI1 as a possible biomarker for those tumours that could benefit from treatment with BMP agonist small molecules.en_US
dc.description.sponsorshipNational Institute of Health Research (NIHR), Academic Clinical Fellowship (ACF)Medical Research Council (MRC), Clinical Research Training Fellowship (CRTF Ali’s Dream and Charlie’s Challenge Charities
dc.language.isoenen_US
dc.publisherQueen Mary University of London
dc.subjectBiological and Chemical Sciencesen_US
dc.subjectAnammoxen_US
dc.subjectaquatic ecosystemsen_US
dc.titleBMI1-BMP Connection in Medulloblastoma Pathogenesisen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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