Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/42642
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- Title
- Proteomic identification of lynchpin urokinase plasminogen activator receptor protein interactions associated with epithelial cancer malignancy
- Related
- Journal of proteome research, Vol. 6, Issue 3, p.1016-1028
- DOI
- 10.1021/pr060518n
- Publisher
- American Chemical Society
- Date
- 2007
- FoR/RFCD Code(s)
-
030406 Proteins and Peptides
060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)
- Author/Creator
- Saldanha, Rohit G
- Author/Creator
- Molloy, Mark P
- Author/Creator
- Bdeir, Khalil
- Author/Creator
- Cines, Douglas B
- Author/Creator
- Song, Xiaomin
- Author/Creator
- Uitto, Pauliina M
- Author/Creator
- Weinreb, Paul H
- Author/Creator
- Voilette, Shelia M
- Author/Creator
- Baker, Mark S
- Description
- Urokinase plasminogen activator (uPA) and its high affinity receptor (uPAR) play crucial proteolytic and non-proteolytic roles in cancer metastasis. In addition to promoting plasmin-mediated degradation of extracellular matrix barriers, cell surface engagement of uPA through uPAR binding results in the activation of a suite of diverse cellular signal transduction pathways. Because uPAR is bound to the plasma membrane through a glycosyl−phosphatidylinositol anchor, these signalling sequelae are thought to occur through the formation of multi-protein cell surface complexes involving uPAR. To further characterize uPAR-driven protein complexes, we co-immunoprecipitated uPAR from the human ovarian cancer cell line, OVCA 429, and employed sensitive proteomic methods to identify the uPAR-associated proteins. Using this strategy, we identified several known, as well as numerous novel, uPAR associating proteins, including the epithelial restricted integrin, αvβ6. Reverse immunoprecipitation using anti-β6 integrin subunit monoclonal antibodies confirmed the co-purification of this protein with uPAR. Inhibition of uPAR and/or β6 integrin subunit using neutralizing antibodies resulted in the inhibition of uPA-mediated ERK 1/2 phosphorylation and subsequent cell proliferation. These data suggest that the association of β6 integrin (and possibly other lynchpin cancer regulatory proteins) with uPAR may be crucial in co-transmitting uPA signals that induce cell proliferation. Our findings support the notion that uPAR behaves as a lynchpin in promoting tumorigenesis by forming functionally active multiprotein complexes.
- Description
- 13 page(s)
- Subject Keyword
- 030406 Proteins and Peptides
- Subject Keyword
- 060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)
- Subject Keyword
- uPA
- Subject Keyword
- uPAR
- Subject Keyword
- ovarian cancer
- Subject Keyword
- OVCA 429
- Subject Keyword
- αvβ6 integrin
- Subject Keyword
- metastasis
- Subject Keyword
- immunoprecipitation
- Subject Keyword
- ERK 1/2
- Subject Keyword
- proliferation
- Resource Type
- journal article
- Organisation
- Macquarie University. Dept. of Chemistry and Biomolecular Sciences
- Identifier
- http://hdl.handle.net/1959.14/42642
- Identifier
- ISSN:1535-3907
- Identifier
- mq-rm-2007003106
- Language
- eng
- Reviewed
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