Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/97752
Title: Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin
Authors: Tay, Chor Yong
Chong, Han Chung
Loo, Say Chye Joachim
Leong, David Tai Wei
Fang, W.
Setyawati, M. I.
Chia, S. L.
Goh, S. L.
Neo, M. J.
Tan, S.M.
Ng, K. W.
Xie, J. P.
Ong, C. N.
Tan, N. S.
Keywords: DRNTU::Engineering::Materials::Nanostructured materials
Issue Date: 2013
Source: Setyawati, M., Tay, C. Y., Chia, S., Goh, S., Fang, W., Neo, M., et al. (2013). Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin. Nature communications, 4, 1673-.
Series/Report no.: Nature communications
Abstract: The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells’ adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as β-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.
URI: https://hdl.handle.net/10356/97752
http://hdl.handle.net/10220/18159
ISSN: 2041-1723
DOI: 10.1038/ncomms2655
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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