The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9



Morgan, MR ORCID: 0000-0001-7728-9883, Thomas, GJ, Russell, A, Hart, IR and Marshall, JF
(2004) The integrin cytoplasmic-tail motif EKQKVDLSTDC is sufficient to promote tumor cell invasion mediated by matrix metalloproteinase (MMP)-2 or MMP-9. JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (25). pp. 26533-26539.

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Abstract

Integrins promote cellular invasion through a combination of activities, including adhesion to an extracellular matrix ligand, which result in the generation of intracellular signals that lead to changes in cell behavior. Until now, there have been no data that identify a particular region of the cytoplasmic tail of integrin subunits as being responsible specifically for promoting the invasive activity of tumor cells. In this report, we show that amino acids with the sequence EKQKVDLSTDC, which are the C-terminal residues of the integrin beta6 subunit, promote alphavbeta6-dependent invasion in a matrix metalloproteinase (MMP)-9-dependent fashion. This same peptide sequence, when expressed at the cytoplasmic end of the beta3 integrin subunit, was able to enhance alphavbeta3-mediated invasive and enzymatic activity of tumor cells in an MMP-2-dependent fashion. Our results show that these 11 amino acids, when expressed at the C terminus of the beta subunit, are responsible for regulating the activity of invasion-promoting degradative enzymes, whereas the specific MMP involved in this cellular behavior is dependent on the context of the remainder of the beta integrin subunit.

Item Type: Article
Additional Information: ## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: Cell Line, Tumor, Extracellular Matrix, Cytoplasm, Humans, Neoplasm Invasiveness, Collagen, Proteoglycans, Amino Acids, Vitronectin, Laminin, Integrins, Drug Combinations, Ligands, Microscopy, Fluorescence, Fluorescent Antibody Technique, Indirect, Flow Cytometry, Transfection, Cell Movement, Gene Expression Regulation, Neoplastic, Up-Regulation, Amino Acid Sequence, Amino Acid Motifs, Protein Structure, Tertiary, Protein Binding, Molecular Sequence Data, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9
Depositing User: Symplectic Admin
Date Deposited: 17 Nov 2016 14:49
Last Modified: 19 Jan 2023 07:25
DOI: 10.1074/jbc.M401736200
Open Access URL: http://www.jbc.org/content/279/25/26533.full
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3004570