Prostate cancer metastasis is a complex process, involving multiple pathways in its orchestration. Malignant cells are influenced by different growth factors from the extracellular environment which promote or inhibit cell movement and metastasis. HGF has been implicated in progression and metastasis of prostate cancer. A cell interacts with the environment through surface molecules like integrins. These interactions are further translated in to different responses through various intracellular machineries. Furthermore organization of the actin cytoskeleton is vital for many cellular functions. WAVEs are member of WASP family of proteins, which have important role in regulation of actin dynamics through regulation of actin related protein (ARP 2/3). The role of individual members of WASP family has been investigated in development and progression of different cancers. We documented the expression of different WAVE family members in various prostate cancer cell lines. Expression of WAVE-3 was effectively knocked down with the use of hammer head ribozymes. Loss of WAVE-3 expression resulted in reduced cell movement and invasion in the PC-3 cell line. These cells failed to show any significant increase in cellular movement and invasive potential following treatment with HGF. Further experiments to investigate the underlying mechanism of this phenotypic change revealed that optimum levels of phosphorylated paxillin play an important role in this change. Our study also indicates that reduced potential of invasive capability following WAVE-3 knock down, may be related to reduced availability of MMP-2 in the cellular environment.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:611047 |
| Date | January 2014 |
| Creators | Moazzam, Muhammad |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/60160/ |
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