Please use this identifier to cite or link to this item: https://doi.org/10.1182/blood-2011-01-328716
Title: ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters
Authors: Huang, R.-L.
Teo, Z.
Chong, H.C.
Zhu, P.
Tan, M.J.
Tan, C.K.
Lam, C.R.I.
Sng, M.K.
Leong, D.T.W. 
Tan, S.M.
Kersten, S.
Ding, J.L. 
Li, H.Y.
Tan, N.S.
Issue Date: 6-Oct-2011
Source: Huang, R.-L., Teo, Z., Chong, H.C., Zhu, P., Tan, M.J., Tan, C.K., Lam, C.R.I., Sng, M.K., Leong, D.T.W., Tan, S.M., Kersten, S., Ding, J.L., Li, H.Y., Tan, N.S. (2011-10-06). ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters. Blood 118 (14) : 3990-4002. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2011-01-328716
Abstract: Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted C-terminal fibrinogen-like domain of angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial because of the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with 3 novel binding partners, integrin α5β1, VE-cadherin, and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin α5β1-mediated Rac1/PAK signaling to weaken cell-cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies. © 2011 by The American Society of Hematology.
Source Title: Blood
URI: http://scholarbank.nus.edu.sg/handle/10635/51753
ISSN: 00064971
DOI: 10.1182/blood-2011-01-328716
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

76
checked on Dec 13, 2017

WEB OF SCIENCETM
Citations

70
checked on Nov 14, 2017

Page view(s)

38
checked on Dec 9, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.