Abstract：
: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 proinvasive 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.
journal_name
Celljournal_title
Cellauthors
Boire A,Covic L,Agarwal A,Jacques S,Sherifi S,Kuliopulos Adoi
10.1016/j.cell.2004.12.018subject
Has Abstractpub_date
2005-02-11 00:00:00pages
303-13issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(04)01210-3journal_volume
120pub_type
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