Analysis of the TGF induced enhancement of procollagen I secretion
Collagen is the most abundant protein in mammals: it is essential for tissue development and homeostasis, and its dysfunction contributes to tumor progression. As a major component of the extracellular matrix (ECM), collagen is secreted by specialized cells such as fibroblasts. In the tumor microenvironment, transforming growth factor- (TGF) released by tumors can stimulate fibroblasts to produce more collagen, among many other proteins. In a recent study, when TGF was supplemented to cultured fibroblasts, transcription of procollagen I (PC1) more than doubled and so did the amount incorporated into the ECM. I hypothesize that, in response to increased synthesis, the secretory pathway is upregulated to more efficiently transport PC1 out of the cell, where it is incorporated into the ECM. I will measure the expression level of secretory proteins that are necessary for PC1 secretion by immunoblotting, and elevated expression would be consistent with my hypothesis. In a parallel experiment, I will study by immunofluorescence microscopy whether secretory organelles are enlarged to accommodate the increased production of secretory cargos. Together, I aim to examine the mechanisms involved in enhancement of collagen deposition by TGF. This will help us better understand the role of collagen secretion within the tumor microenvironment.
Message to Sponsor
- Major: Molecular and Cell Biology, Economics
- Sponsor: Rose Hills Experience
- Mentor: Randy Schekman