The Role of the C-Terminal Lysine of S100P in S100P-Induced Cell Migration and Metastasis

Ismail, Thamir M ORCID: 0000-0001-5624-6593, Gross, Stephane R, Lancaster, Tara, Rudland, Philip S ORCID: 0000-0002-7491-0846 and Barraclough, Roger ORCID: 0000-0002-7203-1194 (2021) The Role of the C-Terminal Lysine of S100P in S100P-Induced Cell Migration and Metastasis. BIOMOLECULES, 11 (10). 1471-.

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Official URL: http://dx.doi.org/10.3390/biom11101471

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	S100P, membrane, metastasis, cell migration, myosin llA
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	09 Dec 2021 08:19
Last Modified:	08 Mar 2023 12:00
DOI:	10.3390/biom11101471
Open Access URL:	https://www.mdpi.com/2218-273X/11/10/1471
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3140921