title: Wnt/beta-catenin signaling pathway as a novel cancer drug target.
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 beta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. Deregulation of the canonical Wnt/beta-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of beta-catenin, has been implicated in colorectal tumorigenesis. Although oncogenic mutations of beta-catenin have only been discovered in a small fraction of non-colon cancers, elevated levels of beta-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 beta-catenin/Tcf transactivation complex. Given the fact that Wnt/beta-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/beta-catenin signaling pathway in rational cancer drug discovery.
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rayburn
authors.forename: Quan
authors.initials: Q
authors.lastname: Kang
authors.forename: Weike
authors.initials: W
authors.lastname: Si
authors.forename: Jong Kyung
authors.initials: JK
authors.lastname: Park
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin