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dc.contributor.authorBASKARAN, PRITHTHIVIKAen_US
dc.descriptionPhD thesisen_US
dc.description.abstractSolid tumours are composed of cancer cells and a variety of other cell types, forming the tumour microenvironment (TME). Cells within the TME promote cell survival, proliferation and epithelial-mesenchymal transition (EMT) of cancer cells. Among the key metastasis-inducing cellular components of the TME are cancer-associated fibroblasts (CAFs), which are activated by cancer cells through release of factors such as TGFβ. Here we sought to delineate the role of the PKN kinases in breast cancer with a focus on mesenchymal-phenotype TNBC models and subsequently in CAFs. This study was motivated by the critical roles identified for PKN2 in mesenchymal cells during development, as well as in cell behaviours critically hijacked during breast cancer development and progression. TNBC cells with mesenchymal-like morphologies (SUM159 and MDAMB231) showed reduced survival with PKN2 and PKN3 knockdown. This corroborated with previous finding where loss of PKN2 reduced proliferation of mice embryonic fibroblasts (MEFs) and systemic PKN2 knockout resulted in impaired development of the mesenchyme in mouse embryo. Therefore, subsequent studies in this project investigated the role of PKN2 in fibroblasts and their interaction with cancer cells. The importance of the stroma in breast cancer has been demonstrated in several studies. The presence of stroma/desmoplasia in triple-negative breast cancer (TNBC) has been linked to bad prognosis, which is also contradicted in other studies. Our laboratory identified several cancer-associated roles for PKN2 in pancreatic fibroblasts, including activation and reciprocal signalling to cancer cells to promote proliferation and invasion. Data from this project indicate dependency on PKN2 for fibroblast activation. Subsequently, a panel of genes associated with PKN2-dependent fibroblast activation was selected to investigate the clinical relevance of PKN2 in breast cancer stroma. Furthermore, stromal deletion of PKN2 in a mouse orthotopic model resulted in tumours with reduced fibrotic stroma and decreased vasculature.en_US
dc.description.sponsorshipMedical Research Council (grant number: MR/K501372/1)en_US
dc.rightsThe 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
dc.titleExploring the roles of the Protein Kinase N family in breast canceren_US
pubs.notesNot knownen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US

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  • Theses [3709]
    Theses Awarded by Queen Mary University of London

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