Abstract |
Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell-cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 supports β1 integrin- and syndecan-4 (Syn4)-mediated contractility-dependent mechanosignalling of melanoma cells. At the single-molecule level, Thy-1 is capable of independently binding α5β1 integrin and syndecan-4 (Syn4) receptors. However, in the presence of both α5β1 and Syn4, the two receptors bind cooperatively to Thy-1, to form a trimolecular complex. This trimolecular complex displays a unique phenomenon we coin 'dynamic catch', characterized by abrupt bond stiffening followed by the formation of catch bonds, where force prolongs the bond lifetime. Thus, we reveal a new class of trimolecular interactions where force strengthens the synergistic binding of two co-receptors and modulates downstream mechanosignalling.
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Authors | Vincent F Fiore, Lining Ju, Yunfeng Chen, Cheng Zhu, Thomas H Barker |
Journal | Nature communications
(Nat Commun)
Vol. 5
Pg. 4886
(Sep 12 2014)
ISSN: 2041-1723 [Electronic] England |
PMID | 25216363
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Integrin alpha5beta1
- Integrin beta1
- Recombinant Proteins
- Syndecan-4
- Thy-1 Antigens
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Topics |
- Biomechanical Phenomena
- Cell Adhesion
- Cell Line, Tumor
- Gene Expression
- Humans
- Integrin alpha5beta1
(chemistry, genetics, metabolism)
- Integrin beta1
(chemistry, genetics, metabolism)
- K562 Cells
- Mechanotransduction, Cellular
- Protein Binding
- Protein Folding
- Recombinant Proteins
(chemistry, genetics, metabolism)
- Syndecan-4
(chemistry, genetics, metabolism)
- Tensile Strength
- Thy-1 Antigens
(chemistry, genetics, metabolism)
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