Clarke, Christopher J, Gross, Stephane R, Ismail, Thamir M ORCID: 0000-0001-5624-6593, Rudland, Philip S ORCID: 0000-0002-7491-0846, Al-Medhtiy, Morteta, Santangeli, Michael and Barraclough, Roger ORCID: 0000-0002-7203-1194
(2017)
Activation of tissue plasminogen activator by metastasis-inducing S100P protein.
BIOCHEMICAL JOURNAL, 474 (19).
pp. 3227-3240.
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Abstract
S100P protein in human breast cancer cells is associated with reduced patient survival and, in a model system of metastasis, it confers a metastatic phenotype upon benign mammary tumour cells. S100P protein possesses a C-terminal lysine residue. Using a multiwell <i>in vitro</i> assay, S100P is now shown for the first time to exhibit a strong, C-terminal lysine-dependent activation of tissue plasminogen activator (tPA), but not of urokinase-catalysed plasminogen activation. The presence of 10 μM calcium ions stimulates tPA activation of plasminogen 2-fold in an S100P-dependent manner. S100P physically interacts with both plasminogen and tPA <i>in vitro</i>, but not with urokinase. Cells constitutively expressing S100P exhibit detectable S100P protein on the cell surface, and S100P-containing cells show enhanced activation of plasminogen compared with S100P-negative control cells. S100P shows C-terminal lysine-dependent enhancement of cell invasion. An S100P antibody, when added to the culture medium, reduced the rate of invasion of wild-type S100P-expressing cells, but not of cells expressing mutant S100P proteins lacking the C-terminal lysine, suggesting that S100P functions outside the cell. The protease inhibitors, aprotinin or α-2-antiplasmin, reduced the invasion of S100P-expressing cells, but not of S100P-negative control cells, nor cells expressing S100P protein lacking the C-terminal lysine. It is proposed that activation of tPA via the C-terminal lysine of S100P contributes to the enhancement of cell invasion by S100P and thus potentially to its metastasis-promoting activity.
Item Type: | Article |
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Uncontrolled Keywords: | Cell Line, Tumor, Animals, Rats, Neoplasm Invasiveness, Neoplasm Metastasis, Cations, Divalent, Calcium, Plasminogen, Tissue Plasminogen Activator, Calcium-Binding Proteins, Neoplasm Proteins, Protease Inhibitors, Mutation |
Depositing User: | Symplectic Admin |
Date Deposited: | 18 Sep 2018 09:26 |
Last Modified: | 19 Jan 2023 01:17 |
DOI: | 10.1042/BCJ20170578 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3026433 |
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- Activation of tissue plasminogen activator by metastasis-inducing S100P protein. (deposited 18 Sep 2018 09:26) [Currently Displayed]