Authors: Miele, Lucio; Golde, Todd; Osborne, Barbara

Source: Current Molecular Medicine, Volume 6, Number 8, December 2006 , pp. 905-918(14)

Publisher: Bentham Science Publishers

Abstract:

The evolutionarily conserved developmental pathway driven by Notch receptors and ligands has acquired multiple post-natal homeostatic functions in vertebrates. Potential roles in human physiology and pathology are being studied by an increasingly large number of investigators. While the canonical Notch signaling pathway is deceptively simple, the consequences of Notch activation on cell fate are complex and context-dependent. The manner in which other signaling pathways cross-talk with Notch signaling appears to be extraordinarily complex. Recent observations have demonstrated the importance of endocytosis, multiple ubiquitin ligases, non-visual β-arrestins and hypoxia in modulating Notch signaling. Structural biology is shedding light on the molecular mechanisms whereby Notch interacts with its nuclear partners. Genomics is slowly unraveling the puzzle of Notch target genes in several systems. At the same time, interest in modulating Notch signaling for medical purposes has dramatically increased. Over the last few years we have learned much about Notch signaling in cancer, immune disorders, neurological disorders and most recently, stroke. The role of Notch signaling in normal and transformed stem cells is under intense investigation. Some Notchmodulating drugs are already in clinical trials, and others at various stages of development. This review will focus on the most recent findings on Notch signaling in cancer and discuss their potential clinical implications.

Keywords: Notch; cancer; gamma-secretase

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156652406779010830

Affiliations: 1: Breast Cancer Program,Cardinal Bernardin Cancer Center, Loyola University Chicago, Building 112, Room 236, 2160 S. 1st Avenue, Maywood, IL 60153, USA.

Publication date: 2006-12-01

More about this publication?

• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

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