Role of Plakoglobin in Breast Cancer Cell Motility and Invasion

摘要

The goal of this project was to determine how plakoglobin (PG) affects cell motility. others in the Brackenbury laboratory previously isolated variants of the PAM2 12 keratinocyte cell line that expressed low levels of plakoglobin, did not form compact colonies, and had lost contact suppression of motility. These findings implied that plakoglobin is a significant regulator of cell movement. I proposed to analyze how plakoglobin exerted its effect, to determine whether plakoglobin acted in a structural capacity, such as a docking protein or signal transducer, or whether it acted as a transcriptional activator, possibly controlling expression of genes required to suppress motility. During the first year of this fellowship, I found that the original PAM2 12 cell model was unsuitable for further investigation and developed a new model system for analysis, in the process verifying that plakoglobin is required for contact regulation of movement. I also characterized a portion of the human plakoglobin gene, correcting a significant error in the literature and produced mutant plakoglobin constructs that will soon be used to analyze how plakoglobin suppresses movement.