PMID- 34015469
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220531
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 85
DP  - 2021 Sep
TI  - Responses of Porcupine and Wntless proteins to oxidative, hypoxic and endoplasmic 
      reticulum stresses.
PG  - 110047
LID - S0898-6568(21)00136-4 [pii]
LID - 10.1016/j.cellsig.2021.110047 [doi]
AB  - The WNT (Wingless and Int-1) proteins play a role in stem cell development and 
      cell differentiation. Mutations in the WNT proteins lead to the development of 
      various tumours, including gastric tumours. Porcupine (PORCN) is a 
      palmitoyltransferase and Wntless (WLS) is a dedicated WNT transport protein that 
      modify and fold the WNT proteins respectively and are involved in their proper 
      secretion and binding to the frizzled (FZD) receptor and the lipoprotein 
      receptor-related protein 5 or 6 (LRP5/6). We investigated how modifications of 
      PORCN and WLS result in changes in WNT expression and secretion from cells under 
      stress conditions that occur in the tumour microenvironment (hypoxia, oxidative 
      stress, endoplasmic reticulum (ER) stress). In the present study, we found the 
      mRNA expression of both PORCN and WLS were significantly increased with 
      treatments inducing oxidative stress (antimycin A) and proteasome inhibition 
      (MG-132), in human colon cancer (HCT116) and human intestinal epithelial cell-6 
      (HIEC-6) cells. Treatment with ER stressors thapsigargin, tunicamycin, and 
      dithiolthreitol significantly increased PORCN gene expression, while treatment 
      with thapsigargin and dithiolthreitol increased WLS gene expression. The 
      expression of PORCN and WLS proteins increased with hypoxia and ER stressor 
      treatments in both HCT116 and HIEC-6 cells. All stressors used in this study 
      increased beta-catenin (beta-catenin) expression in HCT116 cells. Our results 
      suggest that these stressors alter PORCN, WLS and beta-catenin expression and 
      function which may, in turn, alter WNT secretion. Silencing the expression of 
      PORCN and WLS with siRNA expression reduced the expression of WLS and WNT3A in 
      HCT116 cells. The possibility exists that PORCN specifically may be involved in a 
      novel signaling pathway, independent of its palmitoleation of the WNT proteins 
      and its role in their secretion, that is rate-limiting for cancer cell growth and 
      tumorigenesis, within the tumour microenvironment.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Mohamed, Rowida
AU  - Mohamed R
AD  - Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, 
      Ontario K1S 5B6, Canada.
FAU - Kennedy, Catherine
AU  - Kennedy C
AD  - Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, 
      Ontario K1S 5B6, Canada.
FAU - Willmore, William G
AU  - Willmore WG
AD  - Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, 
      Ontario K1S 5B6, Canada; Department of Biology, Carleton University, 1125 Colonel 
      By Drive, Ottawa, Ontario K1S 5B6, Canada; Institute of Biochemistry, Carleton 
      University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic 
      address: Bill.Willmore@carleton.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210517
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (WLS protein, human)
RN  - EC 2.3.- (Acyltransferases)
RN  - EC 2.3.1.- (PORCN protein, human)
SB  - IM
MH  - Acyltransferases/genetics/metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - Humans
MH  - Hypoxia
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Proteins/metabolism
MH  - Oxidative Stress
MH  - Receptors, G-Protein-Coupled
MH  - Wnt Signaling Pathway
OTO - NOTNLM
OT  - Endoplasmic reticulum (ER) stress
OT  - Hypoxia
OT  - Oxidative stress
OT  - Porcupine
OT  - Stress
OT  - Wnt
OT  - Wntless
EDAT- 2021/05/21 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/05/20 20:14
PHST- 2021/03/07 00:00 [received]
PHST- 2021/05/04 00:00 [revised]
PHST- 2021/05/16 00:00 [accepted]
PHST- 2021/05/21 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/05/20 20:14 [entrez]
AID - S0898-6568(21)00136-4 [pii]
AID - 10.1016/j.cellsig.2021.110047 [doi]
PST - ppublish
SO  - Cell Signal. 2021 Sep;85:110047. doi: 10.1016/j.cellsig.2021.110047. Epub 2021 
      May 17.