Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Oscar Aguilera, Alberto Munoz, Manel Esteller and Mario F. Fraga

DOI: 10.2174/187153007780059450

Epigenetic Alterations of the Wnt/β -Catenin Pathway in Human Disease

Page: [13 - 21] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

The Wnt/β-catenin pathway plays critical roles in cell physiology, including determination, proliferation, migration and differentiation in embryonic development and adult homeostasis. Several components of the Wnt/β-catenin pathway, such as SFRPs, WIF-1, DKK-1, APC, AXIN2, ICAT, LEF1 and β-catenin, are the target of mutations or epigenetic inactivation leading to the deregulation or constitutive activation of the Wnt/β-catenin pathway. Aberrant activation of the Wnt signalling pathway abrogates controlled growth and impairs cell differentiation. Alterations of the Wnt signalling pathway have been found in cancer, osteoporosis, ischemic neuronal death and other human diseases. Here we review the alterations of the Wnt/β-catenin signalling cascade and discuss the biological significance and relationship between mutation and/or epigenetic silencing within the same pathway.

Keywords: DNA methylation, CpG dinucleotides, Secreted frizzled-related proteins, Dickkopf (Dkk), Adenomatous polyposis coli (APC)