Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The signaling pathway mediated by Wingless-type (Wnt) proteins is highly conserved in evolution. This pivotal pathway is known to regulate cell fate decisions, cell proliferation, morphology, migration, apoptosis, differentiation and stem cell self-renewal. It currently includes the canonical or Wnt/beta-catenin pathway in which Wnt proteins bind to 'frizzled' receptors, which leads to downstream activation of gene transcription by beta-catenin. Second, the noncanonical or beta-catenin-independent pathways are now known to be mediated by three possible mechanisms: (1) the Wnt/Ca(2+) pathway, (2) the Wnt/G protein signaling pathway, and (3) the Wnt/PCP or planar cell polarity pathway. Wnt signaling is implicated at several stages of mammary gland growth and differentiation, and possibly in the involution of mammary gland following lactation. Recent evidence suggests the role of Wnt signaling in human breast cancer involves elevated levels of nuclear and/or cytoplasmic beta-catenin using immunohistochemistry, overexpression or downregulation of specific Wnt proteins, overexpression of CKII and sFRP4, downregulation of WIF-1 and sFRP1, as well as amplification of DVL-1. Further research is required to determine how Wnt signaling is involved in the development of different histological types of breast cancer and whether it promotes the viability of cancer stem cells or not.
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PMID:Wnt signaling pathway in mammary gland development and carcinogenesis. 1731 92

It has been two decades since investigators discovered the link between the Drosophila wingless (Wg) gene and the vertebrate oncogene int-1, thus establishing the family of signaling proteins known as Wnts. Since the inception of the Wnt signaling field, there have been 19 Wnt isoforms identified in humans. These secreted glycoproteins can activate at least two distinct signaling pathways in vertebrate cells, leading to cellular changes that regulate a vast array of biological processes, including embryonic development, cell fate, cell proliferation, cell migration, stem cell maintenance, tumor suppression, and oncogenesis. In certain contexts, one subset of Wnt isoforms activates the canonical Wnt/beta-catenin pathway that is characterized by the activation of certain beta-catenin-responsive target genes in response to the binding of Wnt ligand to its cognate receptors. Similarly, a second subset of Wnt isoforms activates beta-catenin-independent pathways, including the Wnt/calcium (Wnt/Ca) pathway and the Wnt/planar cell polarity (Wnt/PCP) pathway, in certain cellular contexts. In addition, research has identified several secreted proteins known to regulate Wnt signaling, including the Dickkopf (DKK) family, secreted Frizzled-related proteins (sFRPs), and Wnt inhibitory factor-1 (WIF-1). The advent of technologies that can provide genome-wide expression data continues to implicate Wnts and proteins that regulate Wnt signaling pathways in a growing number of disease processes. The aim of this review is to provide a context on the Wnt field that will facilitate the interpretation and study of Wnt signaling in the context of human disease.
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PMID:A Wnt survival guide: from flies to human disease. 1917 35