A role for FAK in the Concanavalin A-dependent secretion of matrix metalloproteinase-2 and -9

Authors

Thet Thet Sein
Aye Aye Thant
Yukiko Hiraiwa
Arm R. Amin, Marshall UniversityFollow
Yasuyoshi Sohara
Yuzhen Liu
Satoru Matsuda
Tadashi Yamamoto
Michinari Hamaguchi

Document Type

Article

Publication Date

9-2000

Abstract

To study the signaling pathway critical for the secretion of matrix metalloproteinases (MMPs), we examined the role of focal adhesion kinase (FAK) in Concanavalin A (Con A)-stimulated cells. We established a cell line in which FAK gene was conditionally inducible by use of FAK-null ®broblasts and the tetracycline repression system. In this cell line, FAK expression was undetectable in the presence of tetracycline but induced within 1 day by the removal of the drug. We found that FAK expression augmented the Con A-dependent secretion of MMP-9 and MMP-2. In contrast, proteolytic activation of MMP-2 by Con A-treatment did not require FAK expression. In addition, activation of MMP-secretion and tyrosine phosphorylation of FAK by Con A, but not the proteolytic activation of MMP-2, required attachment of the cells to the extracellular matrix. Taken together, our results suggest that the FAK signaling pathway play a pivotal role in the secretion of MMPs.

Comments

Copyright © 2000 Macmillan Publishers Ltd All rights reserved.

Recommended Citation

Thant AA, Nawa A, Kikkawa F, Ichigotani Y, Zhang Y, Sein TT, Amin AR, Hamaguchi M. Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells. Clinical & experimental metastasis. 2000;18(5):423-8.