LIM kinase regulation of cell motility and invasion

Scott, Rebecca Wilson (2010) LIM kinase regulation of cell motility and invasion. PhD thesis, University of Glasgow.

Abstract

This thesis describes how both LIM Kinase 1 and LIM Kinase 2 are both important regulators of cell invasion. Chapter 3 presents data that shows that inhibition of LIMK function blocks the collective invasion of MDA MB 231 breast carcinoma cells in a three-dimensional matrix. Although LIMK was not required for cell motility in two dimensions, a novel role for LIMK in both extracellular matrix degradation and deformation activities was shown in three dimensions in Chapter 4. Consistent with matrix remodeling being a requirement for path generation by leading cells in collective invasion, LIMK activity was also shown to be required by leading cells in MDA MB 231 collective invasion. However, it was also discovered that LIMK activity was not required for path following MDA MB 231. The importance of Cofilin activity as a conduit of LIMK activity during invasion was investigated in Chapter 5, a well as potential novel protein interactions of Cofilin. The identification of novel substrates of LIMK was attempted in Chapter 6, leaving prospective routes of investigation to further elucidate the roles of LIMK1 and LIMK2 in cells.
The main findings presented in this thesis reveal a requirement for LIMK activity in the path generation function of leading cells in collective invasion. Given that individual invading cells must generate their own paths, these results lend support to the continued development of LIMK inhibitors to counter tumor cell invasion and metastasis.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: LIM Kinase, Cancer, Invasion, Motility
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Michael, Prof. Olson
• Date of Award: 2010
• Depositing User: Miss Rebecca W Scott
• Unique ID: glathesis:2010-2247
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 09 Nov 2010
• Last Modified: 10 Dec 2012 13:53
• URI: https://theses.gla.ac.uk/id/eprint/2247