Electronic Thesis and Dissertation Repository

MT1-MMP enhances cell survival and proliferation via roles unrelated to metabolic transcript levels in MCF7 breast cancer cells

Rachel A. Wise, The University of Western Ontario

Abstract

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a multifunctional protease implicated in cancer aggressiveness for its ability to promote proliferation, migration, and invasion, particularly at low expression levels. Due to its multidomain structure and cell signalling abilities, MT1-MMP may act as a key regulatory node enhancing ATP production, which may confer further advantages in cell proliferation and motility. Low levels of MT1-MMP that enhance cell growth/movement were examined with respect to cell metabolism. Cells expressing different levels or forms of MT1-MMP were cultured in media containing different metabolites to assess viability, proliferation, and metabolic gene transcript levels. While cells with a cytoplasmic domain deletion in MT1-MMP demonstrated more transcript level changes than cells that differed in MT1-MMP levels, there were no metabolically relevant differences in metabolic gene transcript levels, suggesting MT1-MMP does not modulate key metabolic pathways to confer proliferative advantages.