Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biology

Supervisor(s)

Dr. Sashko Damjanovski

Abstract

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a multifunctional protease that degrades proteins during cell migration, and influences cell survival. Both the protein localization and signal transduction capabilities of MT1-MMP depend on its cytoplasmic domain (CD), indicative of a diverse regulatory function. The effects of CD mutations on cell migration and survival were examined by ectopically expressing MT1-MMP variants in MCF-7 cells. CD alteration by substitution or deletion did not abolish the migration-promoting effects of MT1-MMP, but did decrease cell survival and increase apoptosis. Expression of CD-altered MT1-MMP resulted in a protrusive cell morphology in 3D culture that was lost upon serum starvation. MT1-MMP expression in a chicken embryo tumour model resulted in vascularization of MCF-7 tumours; a phenotype that was partially maintained following expression of MT1-MMP CD variants. These results suggest that the CD regulates MT1-MMP localization in a manner required for cell survival, but is dispensable for cell migration.


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