The role of SLIRP and Notch signalling in colorectal cancer

Patrick Aaron Candy

    Research output: ThesisDoctoral Thesis

    249 Downloads (Pure)

    Abstract

    [Truncated abstract] Colorectal cancer (CRC) is the third most common malignancy and the second highest cause of cancer death, accounting for more than 4000 Australians deaths per year. The majority of patients are diagnosed with advanced disease that carries a poor prognosis. There are few clinically useful biomarkers for prediction of CRC disease outcome or new therapies which target specific signalling pathways. Thus, there is a pressing need to identify novel biomarkers and characterise new potential therapeutic targets to provide a foundation for innovative approaches to address the issue of CRC mortality. The nuclear receptor (NR) superfamily of ligand-inducible transcription factors plays an important role in CRC oncogenesis. For example, the NR retinoic acid (RA) receptor alpha (RARα) is highly expressed in colorectal mucosa and cancer and promotes the oncogenic Notch signalling pathway, in particular expression of Notch-induced transcription factors (NTFs) HES1 and SOX9. As aberrant Notch signalling has been implicated in promotion of epithelial to mesenchymal transition (EMT), chemoresistance and metastasis in CRC, identification of factors capable of suppressing both the NR (RARα) and Notch signalling pathways would present new opportunities for CRC treatment. The NR coregulators modulate ("fine-tune") NR activity and play important roles in oncogenesis.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2013

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