Notch signalling is a key pathway controlling angiogenesis in normal tissues and tumours. This has become a major focus of development of anticancer therapy, but to develop this appropriately, we need further understanding of the mechanisms of regulation of Dll4 (Delta-like ligand 4), a key endothelial Notch ligand. Dll4 and VEGF (vascular endothelial growth factor) cross-talk, with VEGF up-regulation of Dll4 and Dll4 down-regulating VEGFR (VEGF receptor) signalling. Both are essential for normal angiogenesis, and blockade of one may produce compensatory changes in the other. The present review considers recent developments in the regulation of Dll4 expression and functions, its role as a mechanism of resistance to anti-angiogenic therapy, and methods needed to develop effective therapy against this target.
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December 2011
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Conference Article|
November 21 2011
New pathways and mechanisms regulating and responding to Delta-like ligand 4–Notch signalling in tumour angiogenesis
Chern Ein Oon;
Chern Ein Oon
1Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, U.K.
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Adrian L. Harris
Adrian L. Harris
1
1Molecular Oncology Laboratories, Department of Oncology, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, U.K.
1To whom correspondence should be addressed (email aharris.lab@imm.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
September 06 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (6): 1612–1618.
Article history
Received:
September 06 2011
Citation
Chern Ein Oon, Adrian L. Harris; New pathways and mechanisms regulating and responding to Delta-like ligand 4–Notch signalling in tumour angiogenesis. Biochem Soc Trans 1 December 2011; 39 (6): 1612–1618. doi: https://doi.org/10.1042/BST20110721
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