Authors: Hue H. Luu; Ruiwen Zhang; Rex C. Haydon; Elizabeth Rayburn; Quan Kang; Weike Si; Jong K. Park; Hui Wang; Ying Peng; Wei Jiang; Tong- C.h.u.a.n. He

Source: Current Cancer Drug Targets, Volume 4, Number 8, December 2004 , pp. 653-671(19)

Publisher: Bentham Science Publishers

Abstract:

Wnt proteins are a large family of secreted glycoproteins. Wnt proteins bind to the Frizzled receptors and LRP5/6 co-receptors, and through stabilizing the critical mediator -catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. Deregulation of the canonical Wnt/-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of -catenin, has been implicated in colorectal tumorigenesis. Although oncogenic mutations of -catenin have only been discovered in a small fraction of non-colon cancers, elevated levels of - catenin protein, a hallmark of activated canonical Wnt pathway, have been observed in most common forms of human malignancies, indicating that activation of this pathway may play an important role in tumor development. Over the past 15 years, our understanding of this signaling pathway has significantly improved with the identification of key regulatory proteins and the important downstream targets of -catenin/Tcf transactivation complex. Given the fact that Wnt/-catenin signaling is tightly regulated at multiple cellular levels, the pathway itself offers ample targeting nodal points for cancer drug development. In this review, we discuss some of the strategies that are being used or can be explored to target key components of the Wnt/- catenin signaling pathway in rational cancer drug discovery.

Keywords: wnt; catenin; signal transduction; tumorigenesis; cancer targets; high throughput screening

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009043332709

Affiliations: 1: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL 60637, USA.

Publication date: 2004-12-01

More about this publication?

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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