{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:35:40Z","timestamp":1780583740754,"version":"3.54.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016133","name":"James Tudor Foundation","doi-asserted-by":"publisher","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}],"id":[{"id":"10.13039\/501100016133","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cancer and Polio Research Fund Ltd.","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"name":"ARCHA at Aston University","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"name":"The Aston University Life and Health Sciences Ph.D. studentship scheme","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"name":"The Biomedical Sciences Research Funding Scheme at Aston University","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>S100P protein is a potent inducer of metastasis in a model system, and its presence in cancer cells of patients is strongly associated with their reduced survival times. A well-established Furth Wistar rat metastasis model system, methods for measuring cell migration, and specific inhibitors were used to study pathways of motility-driven metastasis. Cells expressing C-terminal mutant S100P proteins display markedly-reduced S100P-driven metastasis in vivo and cell migration in vitro. These cells fail to display the low focal adhesion numbers observed in cells expressing wild-type S100P, and the mutant S100P proteins exhibit reduced biochemical interaction with non-muscle myosin heavy chain isoform IIA in vitro. Extracellular inhibitors of the S100P-dependent plasminogen activation pathway reduce, but only in part, wild-type S100P-dependent cell migration; they are without effect on S100P-negative cells or cells expressing C-terminal mutant S100P proteins and have no effect on the numbers of focal adhesions. Recombinant wild-type S100P protein, added extracellularly to S100P-negative cells, stimulates cell migration, which is abolished by these inhibitors. The results identify at least two S100P-dependent pathways of migration, one cell surface and the other intracellularly-linked, and identify its C-terminal lysine as a target for inhibiting multiple migration-promoting activities of S100P protein and S100P-driven metastasis.<\/jats:p>","DOI":"10.3390\/biom11101471","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T10:36:57Z","timestamp":1633516617000},"page":"1471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of the C-Terminal Lysine of S100P in S100P-Induced Cell Migration and Metastasis"],"prefix":"10.3390","volume":"11","author":[{"given":"Thamir M.","family":"Ismail","sequence":"first","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane R.","family":"Gross","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2872-4794","authenticated-orcid":false,"given":"Tara","family":"Lancaster","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Rudland","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-1194","authenticated-orcid":false,"given":"Roger","family":"Barraclough","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ejso.2007.04.009","article-title":"A review of the S100 proteins in cancer","volume":"34","author":"Salama","year":"2007","journal-title":"Eur. 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