Journal
CELL
Volume 120, Issue 3, Pages 303-313Publisher
CELL PRESS
DOI: 10.1016/j.cell.2004.12.018
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL64701] Funding Source: Medline
Ask authors/readers for more resources
Protease-activated receptors (PARs) are a unique class of G protein-coupled receptors that play critical roles in thrombosis, inflammation, and vascular biology. PAR1 is proposed to be involved in the invasive and metastatic processes of various cancers. However, the protease responsible for activating the pro-invasive functions of PAR1 remains to be identified. Here, we show that expression of PAR1 is both required and sufficient to promote growth and invasion of breast carcinoma cells in a xenograft model. Further, we show that the matrix metalloprotease, MMP-1, functions as a protease agonist of PAR1 cleaving the receptor at the proper site to generate PAR1-dependent Ca2+ signals and migration. MMP-1 activity is derived from fibroblasts and is absent from the breast cancer cells. These results demonstrate that MMP-1 in the stromal-tumor microenvironment can alter the behavior of cancer cells through PAR1 to promote cell migration and invasion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available