LIM Kinase 1 (LIMK1), a serine/threonine kinase, modulates actin polymerization and microtubule assembly. The function of LIMK1 is regulated by kinases that are activated by Rho and Rac GTPases. LIMK1 is overexpressed in various cancerous cell types and tissues and its overexpression promotes increased invasion and metastasis of breast and prostate cancer cells. Membrane-Type Matrix Metalloproteinase 1 (MT1-MMP) is a member of the zinc-binding collagenase family, which is involved in extracellular matrix breakdown and activation of secreted MMP-2. The balance between activation and inhibition of MT1- MMP and MMP-2 helps maintaining normal extracellular matrix turnover. However, it has been shown that elevated MT1-MMP expression can cause excessive ECM digestion and promote tumor invasion and metastasis. Since RhoA and Rac1 have been implicated in metastasis and invasion along with LIMK1 activation, we investigated a possible link between LIMK1 and MT1-MMP. Our results show that the level of MT1-MMP expression is correlated with that of LIMK1 and LIMK1 acts as a transcriptional regulator of MT1-MMP. Additionally, we show that LIMK1 physically associates with MT1-MMP and promotes its translocation to the plasma membrane.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd-3410 |
| Date | 01 January 2012 |
| Creators | Ottman, Richard |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations |
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