Please use this identifier to cite or link to this item: https://doi.org/10.1038/cddis.2011.37
Title: Isthmin exerts pro-survival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state
Authors: Zhang, Y. 
Chen, M.
Venugopa, S.L.
Zhou, Y. 
Xiang, W. 
Li, Y.-H.
Lin, Q. 
Kini, R.M. 
Chong, Y.-S.
Ge, R. 
Keywords: Angiogenesis
Apoptosis
Integrin-mediated death
Isthmin
Physical state
Issue Date: May-2011
Source: Zhang, Y., Chen, M., Venugopa, S.L., Zhou, Y., Xiang, W., Li, Y.-H., Lin, Q., Kini, R.M., Chong, Y.-S., Ge, R. (2011-05). Isthmin exerts pro-survival and death-promoting effect on endothelial cells through alphavbeta5 integrin depending on its physical state. Cell Death and Disease 2 (5) : -. ScholarBank@NUS Repository. https://doi.org/10.1038/cddis.2011.37
Abstract: Isthmin (ISM) is a 60 kDa secreted-angiogenesis inhibitor that suppresses tumor growth in mouse and disrupts vessel patterning in zebrafish embryos. It selectively binds to alphavbeta5 (avb5) integrin on the surface of endothelial cells (ECs), but the mechanism of its antiangiogenic action remains unknown. In this work, we establish that soluble ISM suppresses in vitro angiogenesis and induces EC apoptosis by interacting with its cell surface receptor avb5 integrin through a novel 'RKD' motif localized within its adhesion-associated domain in MUC4 and other proteins domain. ISM induces EC apoptosis through integrinmediated death (IMD) by direct recruitment and activation of caspase-8 without causing anoikis. On the other hand, immobilized ISM loses its antiangiogenic function and instead promotes EC adhesion, survival and migration through avb5 integrin by activating focal adhesion kinase (FAK). ISM unexpectedly has both a pro-survival and death-promoting effect on ECs depending on its physical state. This dual function of a single antiangiogenic protein may impact its antiangiogenic efficacy in vivo. © 2011 Macmillan Publishers Limited All rights reserved.
Source Title: Cell Death and Disease
URI: http://scholarbank.nus.edu.sg/handle/10635/53006
ISSN: 20414889
DOI: 10.1038/cddis.2011.37
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