SEMINAR: Targeting Cancer Stem Cells Via Wnt/�-Catenin Antagonist, Secreted Frizzled Related Protein-4

The Speaker: Professor Arun Dharmarajan obtained his PhD from the School of Anatomy, Physiology and Human Biology (then Department of Anatomy and Human Biology), University of Western Australia and carried out his postdoctoral position followed by faculty positions at The Johns Hopkins School of Medicine, Baltimore, USA. He spent the last 20 years in the School of Anatomy, Physiology and Human Biology and is currently professor at the School of Biomedical Sciences, Curtin University. His interests are Wnt signalling in particular a Wnt antagonist, Secreted Frizzled Related Protein-4 (sFRP4) and its role in apoptosis, cancer biology and more recently cancer stem cells.

The Seminar: Malignant tumors have a highly tumourigenic subpopulation, termed cancer stem cells (CSCs) that drive tumor formation and proliferation. CSCs, unlike the bulk of the cells within the tumour, are elusive to drug treatment. They are chemo- and radio-resistant and the central cause for tumour initiation and recurrence. These self-renewing cells are responsible for the flare-up of cancer and remission, long after treatment. The existence of CSCs has been confirmed in many tumour types including gliomas, breast, lung, prostate, head and neck, and colon cancers. Wnt/ß-catenin signalling plays a role in the proliferation of tumour cells and tumour progression and frizzled-4, a member of the Wnt signalling family, governs both stemness and invasiveness of glioma stem cells. In a recent study, we demonstrated that a naturally occurring Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), chemosensitizes and inhibits glioma stem cell proliferation by reducing self-renewal and inducing differentiation. In a recent report, we examined the effect of sFRP4 in chemosensitizing the glioma cell line U138MG and glioma stem cells (GSCs) enriched from U138MG to chemotherapeutics. We found that sFRP4 alone, and in combination with either DOX or cisplatin, induced apoptosis and substantially decreased proliferation in a GSC-enriched population.