Loustau, Thomas, Abou-Faycal, Cherine, Erne, William, Wiesch, Pia Abel zur, Ksouri, Ayoub, Imhof, Thomas ORCID: 0000-0002-0554-7617, Moegelin, Matthias, Li, Chengbei, Mathieu, Malaurie, Salome, Nathalie, Cremel, Gerard, Dhaouadi, Sayda, Bouhaouala-Zahar, Balkiss, Koch, Manuel ORCID: 0000-0002-2962-7814 and Orend, Gertraud ORCID: 0000-0003-2522-1195 (2022). Modulating tenascin-C functions by targeting the MAtrix REgulating MOtif, MAREMO. Matrix Biol., 108. S. 20 - 39. AMSTERDAM: ELSEVIER. ISSN 1569-1802

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Abstract

The extracellular matrix molecule Tenascin-C (TNC) promotes cancer and chronic inflammation by multiple mechanisms. Recently, TNC was shown to promote an immune suppressive tumor microenvironment (TME) through binding soluble chemoattracting factors, thus retaining leukocytes in the stroma. TNC also binds to fibronectin (FN) and other molecules, raising the question of a potential common TNC binding mechanism. By sequence comparison of two TNC-interacting domains in FN, the fifth (FN5) and thirteenth (FN13) fibronectin type III domains we identified a MAtrix REgulating MOtif MAREMO or M-motif that is highly conserved amongst vertebrates. By sequence analysis, structural modeling and functional analysis we found also putative M-motifs in TNC itself. We showed by negative staining electron microscopic imaging that the M-motif in FN mediates interactions with FN as well as with TNC. We generated two M-motif mimetic peptides P5 and P13 resembling the M-motif in FN5 and FN13, respectively. By using structural information we modelled binding of these M-motif mimetics revealing a putative MAREMO binding site MBS in FN5 and TN3, respectively overlapping with the M-motif. We further demonstrated that the M-motif mimetic peptides blocked several functions of TNC, such as binding of TNC to FN, cell rounding on a mixed FN/TNC substratum, FN matrix expression and subsequent assembly, TNC-induced signaling and gene expression, TNC chemokine binding and dendritic cell retention, thus providing novel opportunities to inhibit TNC actions. Our results suggest that targeting the MAREMO/MBS interaction could be exploited for reducing inflammation and matrix functions in cancer and fibrosis. (C)& nbsp;2022 Elsevier B.V. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Loustau, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abou-Faycal, CherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erne, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesch, Pia Abel zurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ksouri, AyoubUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imhof, ThomasUNSPECIFIEDorcid.org/0000-0002-0554-7617UNSPECIFIED
Moegelin, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, ChengbeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mathieu, MalaurieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salome, NathalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cremel, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhaouadi, SaydaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bouhaouala-Zahar, BalkissUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDorcid.org/0000-0002-2962-7814UNSPECIFIED
Orend, GertraudUNSPECIFIEDorcid.org/0000-0003-2522-1195UNSPECIFIED
URN: urn:nbn:de:hbz:38-691061
DOI: 10.1016/j.matbio.2022.02.007
Journal or Publication Title: Matrix Biol.
Volume: 108
Page Range: S. 20 - 39
Date: 2022
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1569-1802
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NOVO STRUCTURE PREDICTION; BINDING-SITE; EXTRACELLULAR-MATRIX; CELL-ADHESION; PEP-FOLD; FIBRONECTIN; METASTASIS; EXPRESSION; DOCKING; REPEATMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69106

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