| Author: | Cheng, Ka Ho |
| Title: | Effect of phosphoinositol 3-kinase isoform p110{463} knockdown by siRNA on Zyxin expression and phosphorylation in Glioblastoma multiforme |
| Degree: | M.Sc. |
| Year: | 2015 |
| Subject: | Glioblastoma multiforme. Phosphoinositides. Protein kinases. Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Health Technology and Informatics |
| Pages: | ix, 92 leaves : illustrations (some color) ; 30 cm |
| Language: | English |
| Abstract: | Glioblastoma multiforme(GBM) is a primary brain tumor with poor prognosis due to its highly aggressive migration and invasion abilities. There are several signaling pathways involved in these processes, in which phosphoinositide 3-kinase (PI3K) signaling pathway is one of them. PI3K is a family of lipid kinases that regulate a number of intracellular signaling pathways involved in multiple cellular processes. Various studies have established that PI3K p110δ isoform is involved in regulating glioma cell migration and invasion . Knockdown of PI3K p110δ isoform can reduce the ability of migration and invasion in GBM cell lines. On the other hand, Zyxin is a focal adhesion protein which plays an important role in cell migration process. It has been reported to be deregulated in many kinds of cancer cells including GBM cell lines. Furthermore, the phosphorylation of Zyxin at serine 142 is treated as a key process in regulating the action of Zyxin. A previous proteomic studies implied that PI3K p110δ may be involved in regulating Zyxin function. To understand the mechanisms of Zyxin regulation in GBM, this study aimed to investigate the effect of PI3K p110δ knockdown on Zyxin regulation including its phorphorylation of at serine 142. In this study, we investigated the Zyxin and phospho-Zyxin(ser142) expression induced by the p110δ isoform of class IA PI3K. Experiments were performed by knocking down the PIK3CD gene in the U87, U373 and SK-MG3 cell lines using small interfering RNA comparing with the control. Protein extracted from these cells were detected with Western blot analysis. Our results suggested that Zyxin expression is not directly affected by kncokdown of PI3K p110δ but the phosphorylation of Zyxin at serine 142 is inhibited by the knockdown process. The results suggest that the PI3K p110δ may control the Zyxin function by regulating the phosphorylation of Zyxin but not the production of Zyxin. Our results may provide more information on the role of PI3K in the migration process, and provide shed light on the development of specific inhibitor against new molecular targets to fight against GBM. |
| Rights: | All rights reserved |
| Access: | restricted access |
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| File | Description | Size | Format | |
|---|---|---|---|---|
| b27806777.pdf | For All Users (off-campus access for PolyU Staff & Students only) | 1.63 MB | Adobe PDF | View/Open |
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