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wntβ-catenin signaling in normal and cancer stem cellswntβ-catenin信号在正常和癌症干细胞
Cancers 2011, 3, 2050-2079; doi:10.3390/cancers3022050 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review Wnt/β-catenin Signaling in Normal and Cancer Stem Cells Kenneth C. Valkenburg, Carrie R. Graveel, Cassandra R. Zylstra-Diegel, Zhendong Zhong and Bart O. Williams * Van Andel Research Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI 49503, USA * Author to whom correspondence should be addressed; E-Mail: Bart.williams@. Received: 3 March 2011; in revised form: 12 April 2011 / Accepted: 13 April 2011 / Published: 19 April 2011 Abstract: The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, β-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/β-catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling. Keywords: Wnt; β-catenin; stem cells; cancer stem cells; colon; mammary; prostate; therapeutics 1. Introduction The “cancer stem cell” model postulates that tumors initiate from a sub-population of cancer cells that are pluripotent (cancer stem cells) and that most cells in the tumor are differen
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