PMID- 30790642
OWN - NLM
STAT- MEDLINE
DCOM- 20200424
LR  - 20200424
IS  - 1879-016X (Electronic)
IS  - 0163-7258 (Linking)
VI  - 198
DP  - 2019 Jun
TI  - Modulating Wnt signaling at the root: Porcupine and Wnt acylation.
PG  - 34-45
LID - S0163-7258(19)30029-4 [pii]
LID - 10.1016/j.pharmthera.2019.02.009 [doi]
AB  - Communication between cells occurs through secreted molecules, among which Wnt 
      ligands play a critical role in balancing cell proliferation, differentiation and 
      cellular homeostasis. The action of Wnt signaling can be modulated at several 
      levels, including posttranslational modification of the Wnt ligands, whose 
      acylation is critical for biological activity. At least three enzymes are 
      necessary for Wnt acylation/deacylation: stearoyl CoA desaturase (SCD), porcupine 
      (PORCN) and Notum. At the endoplasmic reticulum (ER), SCD provides the 
      monounsaturated fatty acid to PORCN, which adds it to the Wnt ligand; at the 
      extracellular matrix, the fatty acid is removed by Notum. Obviously, the 
      interplay between these enzymes will define Wnt signaling ligand secretion and 
      activity. Excessive activation of Wnt signaling has been observed in a variety of 
      solid tumors, which has led the pharmaceutical industry to develop specific 
      inhibitors for this pathway that mainly target PORCN, some of which are in early 
      clinical trials. In the central nervous system (CNS), Wnt signaling activation 
      has been shown to have a neuroprotective effect, and conversely, its inhibition 
      induces neurodegeneration, which implies that the inhibition of PORCN in cancer 
      therapies should be used with caution, and the cognitive performance of the 
      patient should be monitored during treatment. This review collects information 
      about the PORCN enzyme in relation to its role in the Wnt pathway through the 
      acylation of Wnt ligands, its inhibition by drugs in the treatment of some 
      cancers, and its putative modulation in the treatment of neurodegenerative 
      diseases.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Torres, Viviana I
AU  - Torres VI
AD  - Centro de Envejecimiento y Regeneracion (CARE Chile-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Santiago, Chile. Electronic address: vtorresa@bio.puc.cl.
FAU - Godoy, Juan A
AU  - Godoy JA
AD  - Centro de Envejecimiento y Regeneracion (CARE Chile-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Santiago, Chile.
FAU - Inestrosa, Nibaldo C
AU  - Inestrosa NC
AD  - Centro de Envejecimiento y Regeneracion (CARE Chile-UC), Departamento de Biologia 
      Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad 
      Catolica de Chile, Santiago, Chile; Center for Healthy Brain Ageing, School of 
      Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, 
      Australia; Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), 
      Universidad de Magallanes, Punta Arenas, Chile. Electronic address: 
      ninestrosa@bio.puc.cl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190218
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Ligands)
RN  - 0 (Membrane Proteins)
RN  - 0 (Wnt Proteins)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
SB  - IM
MH  - Acylation
MH  - Acyltransferases/*metabolism
MH  - Animals
MH  - Humans
MH  - Ligands
MH  - Membrane Proteins/*metabolism
MH  - Neurodegenerative Diseases/metabolism
MH  - Neurogenesis
MH  - Protein Processing, Post-Translational
MH  - Wnt Proteins/*metabolism
MH  - Wnt Signaling Pathway
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - IWP
OT  - LKG974
OT  - Porcupine
OT  - Wnt
OT  - Wnt-C59
EDAT- 2019/02/23 06:00
MHDA- 2020/04/25 06:00
CRDT- 2019/02/22 06:00
PHST- 2018/11/16 00:00 [received]
PHST- 2019/02/12 00:00 [accepted]
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2020/04/25 06:00 [medline]
PHST- 2019/02/22 06:00 [entrez]
AID - S0163-7258(19)30029-4 [pii]
AID - 10.1016/j.pharmthera.2019.02.009 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2019 Jun;198:34-45. doi: 10.1016/j.pharmthera.2019.02.009. Epub 
      2019 Feb 18.