The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins
Open accessAbstract
The binding of urokinase plaminogen activator (uPA) to its cell surface receptor (uPAR; CD87) promotes cell adhesion by increasing the affinity of the receptor for both vitronectin (VN) and integrins. We provide evidence that plasminogen activator inhibitor (PAI)-1 can detach cells by disrupting uPAR–VN and integrin–VN interactions and that it does so by binding to the uPA present in uPA–uPAR–integrin complexes on the cell surface. The detached cells cannot reattach to VN unless their surface integrins are first activated by treatment with MnCl2. Immunoprecipitation and subcellular fractionation experiments reveal that PAI-1 treatment triggers deactivation and disengagement of uPA–uPAR–integrin complexes and their endocytic clearance by the low density lipoprotein receptor–related protein. Transfection experiments demonstrate that efficient cell detachment by PAI-1 requires an excess of matrix-engaged uPA–uPAR–integrin complexes over free engaged integrins and that changes in this ratio alter the efficacy of PAI-1. Together, these results suggest a VN-independent, uPA–uPAR-dependent mechanism by which PAI-1 induces cell detachment. This pathway may represent a general mechanism, since PAI-1 also can detach cells from fibronectin and type-1 collagen. This novel “deadhesive” activity of PAI-1 toward a variety of cells growing on different extracellular matrices may begin to explain why high PAI-1 levels often are associated with a poor prognosis in human metastatic disease.
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Cited by
Emami Nejad, A., Najafgholian, S., Rostami, A., Sistani, A., Shojaeifar, S., Esparvarinha, M., Nedaeinia, R., Haghjooy Javanmard, S., Taherian, M., Ahmadlou, M., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-020-01719-5 · Cited by 693
Lillis, A. P., Van Duyn, L. B., Murphy-Ullrich, J. E., & Strickland, D. K. (2008) · Physiological Reviews · doi:10.1152/physrev.00033.2007 · Cited by 669
CHAPLAIN, M. A. J., & LOLAS, G. (2005) · Mathematical Models and Methods in Applied Sciences · doi:10.1142/s0218202505000947 · Cited by 323
PAI1 mediates fibroblast-mast cell interactions in skin fibrosis
Pincha, N., Hajam, E. Y., Badarinath, K., Batta, S. P. R., Masudi, T., Dey, R., Andreasen, P., Kawakami, T., Samuel, R., George, R., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99088 · Cited by 70
Novel insights into the multifaceted and tissue‐specific roles of the endocytic receptor LRP1
Yamamoto, K., Scilabra, S. D., Bonelli, S., Jensen, A., Scavenius, C., Enghild, J. J., & Strickland, D. K. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107521 · Cited by 47
Metadata
- Authors
- Czekay, R.-P., Aertgeerts, K., Curriden, S. A., & Loskutoff, D. J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-03-03
- Volume
- 160
- Issue
- 5
- Pages
- 781-791
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2131602901
- Cited by
- 304
- References
- 28
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- green
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