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Title: Targeting Polo-like Kinase 1 in Glioma Propagating Cells
Keywords: Stem cells, Cancer and cancer drugs, Gene expression, Cell-based assays, Polo-like kinase 1
Issue Date: 23-Jul-2012
Source: FOONG SHU FEN CHARLENE (2012-07-23). Targeting Polo-like Kinase 1 in Glioma Propagating Cells. ScholarBank@NUS Repository.
Abstract: Patient-derived glioma-propagating cells (GPCs) possess karyotypic aberrations typical of the primary tumor, extensive self-renewal and serial tumor-propagating ability, and reform tumor xenografts that mirror the patients? original profiles. To explore GPC regulatory pathways, we performed a small molecule screen which identified Plk1 as a potential candidate. Plk1 inhibition through pharmacological and genetic approaches led to significant reduction in GPC frequency and proliferation, and G2/M cell cycle arrest with concomitant apoptosis. Importantly, tumor-bearing mice intravenously treated with a Plk1 small molecule inhibitor displayed reduced tumor volumes with increased necrosis. To derive clinical relevance, we tapped into public glioma databases using bioinformatics methods and showed that high PLK1-coexpressed genes stratified patients for poor survival independently of current clinical indicators. Our data implicate Plk1 as an essential regulator of GPC and consequently tumor growth. Furthermore, our data highlights the limitation of relying solely on morphology-based histological methods to diagnose and subsequently treat patients.
Appears in Collections:Master's Theses (Open)

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