The Cytoplasmic Domain of Membrane-type 1 Matrix Metalloproteinase is Required for its Survival-Promoting, but not its Migration-Promoting Function in MCF-7 Breast Cancer Cells
Master of Science
Dr. Sashko Damjanovski
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.
Pelling, Jacob JH, "The Cytoplasmic Domain of Membrane-type 1 Matrix Metalloproteinase is Required for its Survival-Promoting, but not its Migration-Promoting Function in MCF-7 Breast Cancer Cells" (2016). Electronic Thesis and Dissertation Repository. 3813.